Materiały źródłowe

• #1 Myelofibrosis | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/myelofibrosis

  Myelofibrosis sometimes happens on its own. This is called primary myelofibrosis. Sometimes it’s caused by another blood cell condition. When this happens, it’s called secondary myelofibrosis. […] It’s often not clear what causes myelofibrosis. This cancer happens in the bone marrow. Bone marrow is the soft matter inside the bones where blood cells are made. […] Myelofibrosis starts when blood stem cells in the bone marrow develop changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. In healthy blood stem cells, the DNA gives instructions to turn into blood cells in a controlled way. […] In myelofibrosis, the DNA changes give different instructions to the blood stem cells. The changes tell the blood stem cells to make more blood cells than the body needs. The blood cells don’t work like healthy blood cells.

• #2 Myelofibrosis: Symptoms, Types, Prognosis & Treatment

  https://my.clevelandclinic.org/health/diseases/15672-myelofibrosis

  Myelofibrosis is a rare type of blood cancer where your bone marrow (the soft, spongy tissue inside of your bones) is replaced by fibrous scar tissue. […] With myelofibrosis, a change (mutation) in a stem cells DNA causes the cell to become defective, or a cancer cell, instead. The cell multiplies, passing the mutation onto new cells. […] Scientists dont know what causes myelofibrosis, but they know its associated with DNA changes in specific genes. […] About 60% to 65 % of people with myelofibrosis have a mutation in the JAK2 gene. Another 5% to 10% have a mutation in the myeloproliferative leukemia (MPL) gene. A mutation called calreticulin (CALR) accounts for approximately 20% to 25 % of myelofibrosis cases. […] Youre at increased risk of myelofibrosis if: […] You have primary thrombocytosis or polycythemia vera. […] Youve been exposed to ionizing radiation or petrochemicals like benzene or toluene.

• #2 What Is Myelofibrosis? Symptoms, Causes, Diagnosis, Treatment, and Prevention

  https://www.everydayhealth.com/leukemia/what-is-myelofibrosis-symptoms-causes-diagnosis-treatment-and-prevention/

  Scientists have not yet pinpointed the underlying cause of myelofibrosis, but the consensus is that it is not inheritable. […] We believe that myelofibrosis is driven by changes that occur in the genes that control how the bone marrow functions, Dr. Mesa explains. […] These faulty genes make copies of themselves and pass along the defects to new cells. […] Special proteins in the body called Janus-associated kinases (JAKs) are thought to play a key role in the development of myelofibrosis. […] Between 60 and 65 percent of all people with myelofibrosis have a mutation, or defect, in the JAK2 gene. […] Another genetic mutation, in a gene called calreticulin (CALR), is present in about 20 to 25 percent of people with myelofibrosis. […] Between 5 and 10 percent of patients have a mutation in a gene called the myeloproliferative leukemia (MPL) gene.

• #3 Myelofibrosis – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/myelofibrosis

  Myelofibrosis may occur on its own because of certain gene mutations, or it may occur as a result of other blood disorders. […] Primary myelofibrosis is myelofibrosis that develops on its own, due to certain genetic mutations. […] About half of people who have primary myelofibrosis have a mutation in the Janus kinase 2 (JAK2) gene. […] Other people have a mutation in the gene called calreticulin (CALR), which is involved in making proteins that are needed for proper cell function, or in the thrombopoietin receptor gene (MPL), which is involved in cell growth. […] Secondary myelofibrosis occurs as a result of other disorders, particularly other blood disorders such as chronic myeloid leukemia, polycythemia vera, thrombocythemia, multiple myeloma, and lymphoma. […] It may also occur in people with tuberculosis, pulmonary hypertension, systemic lupus erythematosus (lupus), systemic sclerosis, and HIV infection, and in people in whom a cancer has spread to the bones.

• #3 Myelofibrosis: Symptoms, Causes, Diagnosis, and Treatment

  https://www.webmd.com/cancer/myelofibrosis-causes-risk-factors

  Myelofibrosis is a rare kind of blood cancer that starts in your marrow, a spongy tissue inside your bones that makes blood cells. The disease causes scars called fibrosis, which affects how many blood cells your body can make. […] A problem with one of your genes causes your body to make stem cells that dont work the way they should. These are the cells that make blood in your bone marrow. With myelofibrosis, they get inflamed, and scar tissue forms. […] About 90% of people who get this kind of cancer have a change in one of three genes: JAK2, CALR, or MPL. These genes change during your lifetime, but experts dont know why. In most cases, you dont get these gene problems from your parents, and you dont pass them on to your children. […] These faulty genes make copies of themselves. The bad versions spread through your marrow and try to stop your body from making regular blood cells.

• #4 Myelofibrosis: Symptoms, Causes, Diagnosis, and Treatment

  https://www.webmd.com/cancer/myelofibrosis-causes-risk-factors

  Myelofibrosis is a rare kind of blood cancer that starts in your marrow, a spongy tissue inside your bones that makes blood cells. The disease causes scars called fibrosis, which affects how many blood cells your body can make. […] A problem with one of your genes causes your body to make stem cells that dont work the way they should. These are the cells that make blood in your bone marrow. With myelofibrosis, they get inflamed, and scar tissue forms. […] About 90% of people who get this kind of cancer have a change in one of three genes: JAK2, CALR, or MPL. These genes change during your lifetime, but experts dont know why. In most cases, you dont get these gene problems from your parents, and you dont pass them on to your children. […] These faulty genes make copies of themselves. The bad versions spread through your marrow and try to stop your body from making regular blood cells.

• #5 Primary Myelofibrosis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197954-overview

  Approximately 50-60% of patients with primary myelofibrosis have a gain-of-function mutation in the Janus kinase 2 (JAK2) gene, the JAK2 V617F mutation, which leads to increased cytokine responsiveness of myeloid cells. Another 5-10% of patients have somatic mutations of JAK2 exon 12 or activating mutations of the thrombopoietin receptor gene MPL. In two separate studies, Klampfl et al and Nangalia et al found that mutations in the gene encoding calreticulin (CALR) were present in the majority of patients who lacked mutations in JAK2 or MPL. […] No specific risk factors can be identified in most patients with primary myelofibrosis. However, exposure to radiation, Thorotrast contrast agents, and industrial solvents (eg, benzene, toluene) have been associated with increased risk.

• #6 Myelofibrosis – MPN Research Foundation

  https://mpnresearchfoundation.org/primary-myelofibrosis-pmf/

  Researchers believe MF may be caused by abnormal blood stem cells in the bone marrow. […] Recently, researchers have discovered that these diseases may be caused by acquired gene mutations (changes in DNA that not inherited). […] Risk factors associated with MF include: […] Exposure to petrochemicals (e.g., benzene and toluene) and ionizing radiation may increase the risk of developing MF. […] Approximately 50% to 60% of people with MF have a mutation of the JAK2 gene within their blood-forming cells. […] About 23.5% of people with myelofibrosis and essential thrombocythemia have a mutation called Calreticulin, or CALR.

• #7 How Did I Get Myelofibrosis? – HealthTree for Myelofibrosis

  https://healthtree.org/myelofibrosis/community/articles/myelofibrosis-causes

  Myelofibrosis is a rare blood cancer and stem-cell disorder that causes scarring of the bone marrow. Myelo means bone, and fibrosis refers to the development of fibrous scar tissue. […] In myelofibrosis, these stem cells become mutated, although it is not known how these genetic mutations happen. […] No one knows what triggers the start of myelofibrosis. However, researchers have determined that it is not inherited genetically, so it does not run in families. […] Risk factors associated with myelofibrosis include: Age over 65 years (average age of diagnosis is 65 years), Exposure to certain chemicals, such as toluene and benzene, Exposure to very high levels of radiation, Mutation of the Janus kinase 2 (JAK2) gene (50% to 60% of people with myelofibrosis), Mutation of the calreticulin (CALR) gene, Mutation of the myeloproliferative leukemia protein (MPL) gene. […] However, some people with myelofibrosis don’t have any identifiable gene mutations.

• #8 What Is Myelofibrosis? Symptoms, Causes, Diagnosis, Treatment, and Prevention

  https://www.everydayhealth.com/leukemia/what-is-myelofibrosis-symptoms-causes-diagnosis-treatment-and-prevention/

  Scientists have not yet pinpointed the underlying cause of myelofibrosis, but the consensus is that it is not inheritable. […] We believe that myelofibrosis is driven by changes that occur in the genes that control how the bone marrow functions, Dr. Mesa explains. […] These faulty genes make copies of themselves and pass along the defects to new cells. […] Special proteins in the body called Janus-associated kinases (JAKs) are thought to play a key role in the development of myelofibrosis. […] Between 60 and 65 percent of all people with myelofibrosis have a mutation, or defect, in the JAK2 gene. […] Another genetic mutation, in a gene called calreticulin (CALR), is present in about 20 to 25 percent of people with myelofibrosis. […] Between 5 and 10 percent of patients have a mutation in a gene called the myeloproliferative leukemia (MPL) gene.

• #9 What is myelofibrosis? | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/myelofibrosis/what-is-myelofibrosis

  We dont know exactly what causes primary myelofibrosis. Some research suggests that exposure to the chemical benzene may increase your risk of developing myeloproliferative neoplasms. […] Changes in the JAK2, CALR, and MPL genes are seen in people with primary myelofibrosis. […] More than 55 in 100 people (more than 55%) with myelofibrosis have a change in a gene called JAK2. […] Up to 35 in 100 people (up to 35%) have a change in the CALR gene. And about 8 in 100 people (about 8%) have a change in the MLP gene. When the gene becomes mutated your bone marrow may not function correctly. This means scar tissue can build up in your bone marrow. […] Some people with myelofibrosis have a history of essential thrombocythaemia or polycythaemia vera.

• #10 Myelofibrosis: Symptoms, Types, Prognosis & Treatment

  https://my.clevelandclinic.org/health/diseases/15672-myelofibrosis

  Myelofibrosis is a rare type of blood cancer where your bone marrow (the soft, spongy tissue inside of your bones) is replaced by fibrous scar tissue. […] With myelofibrosis, a change (mutation) in a stem cells DNA causes the cell to become defective, or a cancer cell, instead. The cell multiplies, passing the mutation onto new cells. […] Scientists dont know what causes myelofibrosis, but they know its associated with DNA changes in specific genes. […] About 60% to 65 % of people with myelofibrosis have a mutation in the JAK2 gene. Another 5% to 10% have a mutation in the myeloproliferative leukemia (MPL) gene. A mutation called calreticulin (CALR) accounts for approximately 20% to 25 % of myelofibrosis cases. […] Youre at increased risk of myelofibrosis if: […] You have primary thrombocytosis or polycythemia vera. […] Youve been exposed to ionizing radiation or petrochemicals like benzene or toluene.

• #11 Primary myelofibrosis – Wikipedia

  https://en.wikipedia.org/wiki/Primary_myelofibrosis

  Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL genes. […] The underlying cause of PMF is almost always related to an acquired mutation in JAK2, CALR or MPL in a hematopoietic stem/progenitor cell in the bone marrow. There is an association between mutations to the JAK2, CALR, or MPL genes and myelofibrosis. Approximately 90% of those with myelofibrosis have one of these mutations; 10% do not have mutations in these three genes. […] The JAK2 protein is mutated giving risk to a variant protein with an amino acid substitution commonly referred to as V617F; the mutation causing this variant is found in approximately half of individuals with primary myelofibrosis. […] The MPL gene codes for a protein that acts as a receptor for thrombopoietin, a growth factor that enhances production of platelets. A mutation in that gene, resulting in the substitution W515L, results in thrombopoietin receptor that is constitutively active even in the absence of thrompoietin.

• #12 What Is Myelofibrosis? Symptoms, Causes, Diagnosis, Treatment, and Prevention

  https://www.everydayhealth.com/leukemia/what-is-myelofibrosis-symptoms-causes-diagnosis-treatment-and-prevention/

  Scientists have not yet pinpointed the underlying cause of myelofibrosis, but the consensus is that it is not inheritable. […] We believe that myelofibrosis is driven by changes that occur in the genes that control how the bone marrow functions, Dr. Mesa explains. […] These faulty genes make copies of themselves and pass along the defects to new cells. […] Special proteins in the body called Janus-associated kinases (JAKs) are thought to play a key role in the development of myelofibrosis. […] Between 60 and 65 percent of all people with myelofibrosis have a mutation, or defect, in the JAK2 gene. […] Another genetic mutation, in a gene called calreticulin (CALR), is present in about 20 to 25 percent of people with myelofibrosis. […] Between 5 and 10 percent of patients have a mutation in a gene called the myeloproliferative leukemia (MPL) gene.

• #13 Myelofibrosis – Myelodysplastic Syndrome – Symptoms and Causes

  https://massivebio.com/myelofibrosis-and-myelodysplastic-syndrome/

  Myelofibrosis (MF) is a rare disorder in which abnormal blood cells and fibers build up in the bone marrow. Myelofibrosis is part of a group of diseases called myeloproliferative disorders / neoplasms (MPN), and are characterized for abnormal cells which sometimes harbor mutations in the JAK pathway. […] Primary myelofibrosis is a chronic disorder that affects the bone marrow’s ability to produce blood cells. The condition is often associated with genetic mutations, particularly in the JAK2, CALR, and MPL genes. […] Recent research shows that about 50-60% of people with MF have a mutation in a protein called JAK2, a protein that regulates blood cell production. 30% of patients have a mutation in a gene called calreticulin called CALR, 5-10% of patients have mutations in the platelet hormone receptor called MPL. […] Patients with MF are not born with these mutations, but get them throughout their lives. It is important to note that MF is rarely inherited and is not passed from parent to child, but some families seem to develop the disease more easily than others.

• #14 Myelofibrosis (MF) | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/blood-cancer/myelofibrosis-mf

  Myelofibrosis (MF) is a type of blood cancer that affects the bone marrow. Bone marrow is where blood cells are made. In MF, scar tissue builds up inside the bone marrow. This stops the bone marrow from working properly. […] MF can happen in people who have never had problems with their bone marrow before. This is called primary myelofibrosis (pMF). […] MF can develop in people who have essential thrombocythaemia (ET). This is called post-ET myelofibrosis. […] MF can also develop in people who have polycythaemia vera (PV). This is called post-PV myelofibrosis. […] Genes can develop changes over time. Genetic changes do not always cause problems, but they can cause conditions such as MF. […] About 10 in a 100 people (10%) with primary myelofibrosis do not have a change in any of these genes. This is called triple negative MF. […] Some people with MF do not have any of these genetic changes. This is called triple negative MF.

• #15 Primary Myelofibrosis (PMF) – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/myeloproliferative-disorders/primary-myelofibrosis-pmf

  Primary myelofibrosis results from neoplastic transformation of a pluripotent hematopoietic stem cell. […] Mutations of the Janus kinase 2 (JAK2) gene are present in a high proportion of cases of primary myelofibrosis. […] Mutations of the thrombopoietin receptor gene (MPL) or the calreticulin (CALR) gene also may be the cause of primary myelofibrosis. […] However, there are rare cases of primary myelofibrosis in which none of these three mutations are present (triple-negative primary myelofibrosis). […] Myelofibrosis is often primary but may occur secondary to a number of hematologic, malignant, and nonmalignant disorders, including polycythemia vera and essential thrombocytosis. […] Primary myelofibrosis is a clonal hematopoietic stem cell disorder and often involves JAK2, CALR, or MPL mutations.

• #16 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. […] It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. […] Fibrosis of the marrow is always secondary to a primary event which may be clonal or non clonal.

• #17 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. […] Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. […] The exact pathogenesis of MF is not fully understood. However, better understanding of the role of increased JAK-STAT signaling [either through activating mutations (JAK2V617F, MPL515L/K) within the signaling pathway, or mutations involving CALR], the role of deregulated pro-inflammatory cytokine expression, and the impaired bone marrow microenvironment is transforming the treatment approach for MF. […] A major biological hallmark of MF is a significant elevation in circulating pro-inflammatory cytokines.

• #18 https://www.lls.org/myeloproliferative-neoplasms/myelofibrosis

  https://www.lls.org/myeloproliferative-neoplasms/myelofibrosis

  Is a rare type of blood cancer characterized by the buildup of scar tissue, called fibrosis, in the bone marrow. As scar tissue increases, the bone marrow cannot make enough healthy blood cells […] The cause of primary MF is not fully understood. It is a complex disease that may have many contributing factors. Researchers believe that proteins known as Janus kinases (JAKs) are involved. These proteins send signals that affect the production of blood cells in the bone marrow. They also help control the number of red blood cells, white blood cells and platelets. When JAKs are working normally, they help the body make the right number of blood cells. But when too many signals are sent by these proteins, it causes too many blood cells to be made in the bone marrow […] As the mutated overactive blood stem cell divides and makes copies of itself, it multiplies uncontrollably, creating many abnormal megakaryocytes in the bone marrow. (Megakaryocytes are the cells that produce platelets). These abnormal megakaryocytes may change the environment of the bone marrow by releasing cytokines. Some researchers believe this may cause inflammation and stimulate the buildup of fibrous tissue in the bone marrow. The web of fibers inside the bone marrow then becomes thick, like scar tissue. Over time, the fibrous tissue impairs the bone marrows ability to produce normal blood cells, leading to symptoms and complications.

• #19 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Megakaryocytes and platelets form the central arm in myelofibrosis. […] At each of these steps different cytokines, vitamins, hormones and minerals interact to produce the fibrocollagenous matrix. […] Many signals converge to produce TGF- that stimulates marrow fibrosis. […] The major fibrogenic factor, TGF-, is a multifunctional growth factor that is mostly produced by megakaryocytes and platelets in the marrow. TGF- can also be independently produced by metastatic and infiltrating cells of immune origin to stimulate marrow fibrosis. […] Fibrogenic stimuli may originate from neoplastic or nonneoplastic cells that release specific factors such as growth factors, cytokines and chemokines. This leads to proliferation of selective immunophenotype bearing mesenchymal stem cell populations that differentiate to myofibroblasts and fibroblasts that initiate fibrosis.

• #20 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. […] Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. […] The exact pathogenesis of MF is not fully understood. However, better understanding of the role of increased JAK-STAT signaling [either through activating mutations (JAK2V617F, MPL515L/K) within the signaling pathway, or mutations involving CALR], the role of deregulated pro-inflammatory cytokine expression, and the impaired bone marrow microenvironment is transforming the treatment approach for MF. […] A major biological hallmark of MF is a significant elevation in circulating pro-inflammatory cytokines.

• #21 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Megakaryocytes and platelets form the central arm in myelofibrosis. […] At each of these steps different cytokines, vitamins, hormones and minerals interact to produce the fibrocollagenous matrix. […] Many signals converge to produce TGF- that stimulates marrow fibrosis. […] The major fibrogenic factor, TGF-, is a multifunctional growth factor that is mostly produced by megakaryocytes and platelets in the marrow. TGF- can also be independently produced by metastatic and infiltrating cells of immune origin to stimulate marrow fibrosis. […] Fibrogenic stimuli may originate from neoplastic or nonneoplastic cells that release specific factors such as growth factors, cytokines and chemokines. This leads to proliferation of selective immunophenotype bearing mesenchymal stem cell populations that differentiate to myofibroblasts and fibroblasts that initiate fibrosis.

• #22 Primary myelofibrosis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/primary-myelofibrosis?lang=us

  Primary myelofibrosis is a myeloproliferative neoplasm in which the bone marrow is replaced with collagenous connective tissue resulting in progressive fibrosis. […] It is a chronic clonal stem cell disorder of neoplastic megakaryocytes and is considered a BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homologue 1)-negative myeloproliferative disorder. […] Progressive bone marrow fibrosis is the result of collagen produced by non-neoplastic fibroblasts in response to inappropriate release of PDGF and TGF- from the neoplastic megakaryocytes.

• #23 Myelofibrosis Symptoms & Causes – Described by Patients

  https://thepatientstory.com/patient-stories/mpn/myelofibrosis/myelofibrosis-101/symptoms/

  Both the JAK2 and MPL genes provide the instructions for making proteins to promote the division and growth of blood cells. Mutations of both genes lead to an overactivation of the JAK/STAT pathway. This results in an overproduction of megakaryocytes, the hemopoietic cells that lead to the production of blood cells. […] While the overproduction of blood cells is a problem in itself, megakaryocytes also stimulate a different type of cell to release collagen. Typically collagen helps provide structural support to the cells in the bone marrow. However, when produced in abundance, the collagen forms scar tissue in the bone marrow. […] The CALR gene is responsible for providing the instructions for making a protein that has multiple functions. In comparison, the TET2 gene provides the instructions for the production of a protein whose function is unknown. Further research is necessary to identify how the mutation of the CALR and TET2 genes are involved in the development of myelofibrosis.

• #24 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. […] It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. […] Fibrosis of the marrow is always secondary to a primary event which may be clonal or non clonal.

• #25 Primary myelofibrosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/primary-myelofibrosis/

  Primary myelofibrosis is a condition characterized by the buildup of scar tissue (fibrosis) in the bone marrow, the tissue that produces blood cells. […] Mutations in the JAK2, MPL, CALR, and TET2 genes are associated with most cases of primary myelofibrosis. […] The proteins produced from the JAK2 and MPL genes are both part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell’s nucleus. […] Mutations in either the JAK2 gene or the MPL gene that are associated with primary myelofibrosis lead to overactivation of the JAK/STAT pathway. […] Although mutations in the CALR gene and the TET2 gene are relatively common in primary myelofibrosis, it is unclear how these mutations are involved in the development of the condition. […] Some people with primary myelofibrosis do not have a mutation in any of the known genes associated with this condition. Researchers are working to identify other genes that may be involved in the condition.

• #26 Myelofibrosis Symptoms & Causes – Described by Patients

  https://thepatientstory.com/patient-stories/mpn/myelofibrosis/myelofibrosis-101/symptoms/

  Both the JAK2 and MPL genes provide the instructions for making proteins to promote the division and growth of blood cells. Mutations of both genes lead to an overactivation of the JAK/STAT pathway. This results in an overproduction of megakaryocytes, the hemopoietic cells that lead to the production of blood cells. […] While the overproduction of blood cells is a problem in itself, megakaryocytes also stimulate a different type of cell to release collagen. Typically collagen helps provide structural support to the cells in the bone marrow. However, when produced in abundance, the collagen forms scar tissue in the bone marrow. […] The CALR gene is responsible for providing the instructions for making a protein that has multiple functions. In comparison, the TET2 gene provides the instructions for the production of a protein whose function is unknown. Further research is necessary to identify how the mutation of the CALR and TET2 genes are involved in the development of myelofibrosis.

• #27 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #28 Primary Myelofibrosis Diagnosis & Disease Information

  https://www.cancertherapyadvisor.com/ddi/primary-myelofibrosis/

  The cause of primary myelofibrosis is multifactorial. Genetic mutations are the primary driver of abnormal blood cell production. The most frequently identified mutation in primary myelofibrosis is the Janus kinase 2 (JAK2) V617F mutation, which is found in approximately 43% to 57% of patients with primary myelofibrosis. This mutation causes constant activation of the JAK/signal transducer and activator of transcription (JAK-STAT) signaling pathway, which leads to increased production of myeloid cells. In addition, CALR gene mutations are involved in disease pathogenesis in 25% to 30% of cases, whereas MPL gene mutations are found in 5% of patients with primary myelofibrosis. Altogether, these mutations affect normal signaling, which is required for blood cell formation, and cause fibrotic change in the bone marrow. […] Causes of death in patients with primary myelofibrosis include progression to leukemia, cardiovascular events, infections, and bleeding.

• #29 What Causes Myelofibrosis (MF)?

  https://www.voicesofmpn.com/myelofibrosis-causes

  Myelofibrosis (MF) is complex and may have many contributing factors. Scientists think that it may be related to changes in certain genes. These changes are called „mutations.” […] People with MF have bone marrow that does not work correctly. In some people with this condition, mutations may affect the behavior of certain proteins, which causes the bone marrow to make too many or too few blood cells. This imbalance of blood cells may cause some of the symptoms of MF. This often happens even if mutations arent present. […] Another cause of symptoms may be the overproduction of certain proteins called „cytokines.” Cytokines can cause inflammation. When your body has too many cytokines, you may experience itching, night sweats, and some other symptoms of MF.

• #30 Myelofibrosis: Causes, Symptoms, Treatment, and More

  https://www.healthline.com/health/myelofibrosis

  Myelofibrosis (MF) is associated with a genetic mutation in blood stem cells. However, researchers aren’t sure what causes this mutation. […] When the mutated cells replicate and divide, they pass the mutation on to new blood cells. Eventually, the mutated cells overtake the bone marrow’s ability to produce healthy blood cells. […] This usually results in too few red blood cells and too many white blood cells. It also causes scarring and hardening of your bone marrow, which is usually soft and spongy.

• #31 What Is Myelofibrosis? | Jakafi.com

  https://www.jakafi.com/myelofibrosis/what-is-myelofibrosis

  Myelofibrosis is a complex condition that may have many contributing factors. We do know that certain proteins called Janus-associated kinases, or JAKs, are important. JAKs tell blood cells in the bone marrow to divide and grow. […] When JAKs are working normally, they help the body make the right number of blood cells. But when JAKs aren’t working normally, they cause the body to make the wrong number of blood cells. They can also cause bone marrow scarring, an enlarged spleen, and symptoms. […] Mutations, or changes, in genes are thought to be ultimately responsible for MF. The mutations may be in the genes that make JAKs, or the mutations may be in genes that affect how JAKs function. In either case, the mutations cause what is known as overactive JAK signaling. […] MF can develop from other myeloproliferative neoplasms.

• #32 Myelofibrosis – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/myelofibrosis

  Myelofibrosis may occur on its own because of certain gene mutations, or it may occur as a result of other blood disorders. […] Primary myelofibrosis is myelofibrosis that develops on its own, due to certain genetic mutations. […] About half of people who have primary myelofibrosis have a mutation in the Janus kinase 2 (JAK2) gene. […] Other people have a mutation in the gene called calreticulin (CALR), which is involved in making proteins that are needed for proper cell function, or in the thrombopoietin receptor gene (MPL), which is involved in cell growth. […] Secondary myelofibrosis occurs as a result of other disorders, particularly other blood disorders such as chronic myeloid leukemia, polycythemia vera, thrombocythemia, multiple myeloma, and lymphoma. […] It may also occur in people with tuberculosis, pulmonary hypertension, systemic lupus erythematosus (lupus), systemic sclerosis, and HIV infection, and in people in whom a cancer has spread to the bones.

• #33 Myelofibrosis: Types, Symptoms, Causes, Diagnosis, Treatment and More

  https://www.health.com/myelofibrosis-8405280

  Primary myelofibrosis is the most common type and accounts for about 60% of all cases. The condition occurs spontaneously, without an underlying blood or bone marrow disorder or medical condition. Acquired gene mutations cause most cases of primary myelofibrosis, but what causes these gene mutations is unknown. […] Secondary myelofibrosis develops due to an underlying blood or bone marrow disorder most commonly polycythemia vera (PV) or essential thrombocytosis (ET). PV happens when your body produces too many blood cells (primarily red blood cells). ET is a condition that occurs when your body produces too many platelets. In about 10-20% of people with PV or ET, the condition progresses to myelofibrosis.

• #34 Myelofibrosis: Types, Symptoms, Causes, Diagnosis, Treatment and More

  https://www.health.com/myelofibrosis-8405280

  Primary myelofibrosis is the most common type and accounts for about 60% of all cases. The condition occurs spontaneously, without an underlying blood or bone marrow disorder or medical condition. Acquired gene mutations cause most cases of primary myelofibrosis, but what causes these gene mutations is unknown. […] Secondary myelofibrosis develops due to an underlying blood or bone marrow disorder most commonly polycythemia vera (PV) or essential thrombocytosis (ET). PV happens when your body produces too many blood cells (primarily red blood cells). ET is a condition that occurs when your body produces too many platelets. In about 10-20% of people with PV or ET, the condition progresses to myelofibrosis.

• #35 Myelofibrosis | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/myelofibrosis

  Myelofibrosis sometimes happens on its own. This is called primary myelofibrosis. Sometimes it’s caused by another blood cell condition. When this happens, it’s called secondary myelofibrosis. […] It’s often not clear what causes myelofibrosis. This cancer happens in the bone marrow. Bone marrow is the soft matter inside the bones where blood cells are made. […] Myelofibrosis starts when blood stem cells in the bone marrow develop changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. In healthy blood stem cells, the DNA gives instructions to turn into blood cells in a controlled way. […] In myelofibrosis, the DNA changes give different instructions to the blood stem cells. The changes tell the blood stem cells to make more blood cells than the body needs. The blood cells don’t work like healthy blood cells.

• #36 Primary myelofibrosis – Wikipedia

  https://en.wikipedia.org/wiki/Primary_myelofibrosis

  Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL genes. […] The underlying cause of PMF is almost always related to an acquired mutation in JAK2, CALR or MPL in a hematopoietic stem/progenitor cell in the bone marrow. There is an association between mutations to the JAK2, CALR, or MPL genes and myelofibrosis. Approximately 90% of those with myelofibrosis have one of these mutations; 10% do not have mutations in these three genes. […] The JAK2 protein is mutated giving risk to a variant protein with an amino acid substitution commonly referred to as V617F; the mutation causing this variant is found in approximately half of individuals with primary myelofibrosis. […] The MPL gene codes for a protein that acts as a receptor for thrombopoietin, a growth factor that enhances production of platelets. A mutation in that gene, resulting in the substitution W515L, results in thrombopoietin receptor that is constitutively active even in the absence of thrompoietin.

• #37 What is Secondary Myelofibrosis? – HealthTree for Myelofibrosis

  https://healthtree.org/myelofibrosis/community/articles/what-is-secondary-myelofibrosis

  Myelofibrosis (MF) is a complex blood disorder characterized by an enlarged spleen, various blood cell abnormalities, and potential complications such as vascular issues and progression to a more aggressive phase. […] Secondary myelofibrosis (SMF) encompasses a range of conditions where the bone marrow’s ability to produce blood cells is restricted, leading to fibrosis. Due to its multiple causes, it occurs more commonly than primary myelofibrosis. […] Secondary Myelofibrosis is a result of previous damage to the bone marrow, for it to be considered secondary, there must be a health history of any of the following conditions: Key genetic mutations like JAK2V617F, CALR, and MPL, Chronic kidney disease, Long-term chemotherapy use, especially drugs that are poisonous to the blood cells, Hemolytic anemias, Abnormal growth of cells or tissues in the body(?), Leukemia, multiple myeloma, or other blood cancers, Cancer cells that have spread throughout the body, Inflammatory processes that have passed like; granulomas, osteomyelitis, autoimmune disorders, etc, Conditions of the bone marrow, like scars from biopsies, dead tissue or radiation, Bone diseases that affect bone replacement and formation.

• #38 Myelofibrosis – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/myelofibrosis

  Myelofibrosis may occur on its own because of certain gene mutations, or it may occur as a result of other blood disorders. […] Primary myelofibrosis is myelofibrosis that develops on its own, due to certain genetic mutations. […] About half of people who have primary myelofibrosis have a mutation in the Janus kinase 2 (JAK2) gene. […] Other people have a mutation in the gene called calreticulin (CALR), which is involved in making proteins that are needed for proper cell function, or in the thrombopoietin receptor gene (MPL), which is involved in cell growth. […] Secondary myelofibrosis occurs as a result of other disorders, particularly other blood disorders such as chronic myeloid leukemia, polycythemia vera, thrombocythemia, multiple myeloma, and lymphoma. […] It may also occur in people with tuberculosis, pulmonary hypertension, systemic lupus erythematosus (lupus), systemic sclerosis, and HIV infection, and in people in whom a cancer has spread to the bones.

• #39 Myelofibrosis: Types, Symptoms, Causes, Diagnosis, Treatment and More

  https://www.health.com/myelofibrosis-8405280

  Primary myelofibrosis is the most common type and accounts for about 60% of all cases. The condition occurs spontaneously, without an underlying blood or bone marrow disorder or medical condition. Acquired gene mutations cause most cases of primary myelofibrosis, but what causes these gene mutations is unknown. […] Secondary myelofibrosis develops due to an underlying blood or bone marrow disorder most commonly polycythemia vera (PV) or essential thrombocytosis (ET). PV happens when your body produces too many blood cells (primarily red blood cells). ET is a condition that occurs when your body produces too many platelets. In about 10-20% of people with PV or ET, the condition progresses to myelofibrosis.

• #40 What Is Myelofibrosis? | Jakafi.com

  https://www.jakafi.com/myelofibrosis/what-is-myelofibrosis

  MF is a chronic bone marrow condition that is part of a group of diseases called myeloproliferative neoplasms (MPNs). If MF is a person’s first MPN, then it is called primary myelofibrosis. […] In other cases, another MPN, like polycythemia vera (PV) or essential thrombocythemia (ET), can turn into MF. These conditions are called post-PV MF and post-ET MF. About 10-15% of patients with MF have these conditions.

• #41 Primary myelofibrosis – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/myeloproliferative-neoplasms/primary-myelofibrosis/

  Primary myelofibrosis is a rare chronic disorder diagnosed in an estimated 1 per 100,000 population. It can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years. The cause of primary myelofibrosis remains largely unknown. […] Long-term exposure to high levels of benzene or very high doses of ionising radiation may increase the risk of primary myelofibrosis in a small number of cases. Around one third of people with myelofibrosis have been previously diagnosed with polycythaemia (post-polycythaemic myelofibrosis) or essential thrombocythaemia (post-ET myelofibrosis). […] A mutation in JAK2 is found in about 50% of people with primary myelofibrosis. It is unclear at present why some patients with mutations in JAK2 develop myelofibrosis and others don’t.

• #42 Myelofibrosis – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/myelofibrosis

  Myelofibrosis may occur on its own because of certain gene mutations, or it may occur as a result of other blood disorders. […] Primary myelofibrosis is myelofibrosis that develops on its own, due to certain genetic mutations. […] About half of people who have primary myelofibrosis have a mutation in the Janus kinase 2 (JAK2) gene. […] Other people have a mutation in the gene called calreticulin (CALR), which is involved in making proteins that are needed for proper cell function, or in the thrombopoietin receptor gene (MPL), which is involved in cell growth. […] Secondary myelofibrosis occurs as a result of other disorders, particularly other blood disorders such as chronic myeloid leukemia, polycythemia vera, thrombocythemia, multiple myeloma, and lymphoma. […] It may also occur in people with tuberculosis, pulmonary hypertension, systemic lupus erythematosus (lupus), systemic sclerosis, and HIV infection, and in people in whom a cancer has spread to the bones.

• #43 What is Secondary Myelofibrosis? – HealthTree for Myelofibrosis

  https://healthtree.org/myelofibrosis/community/articles/what-is-secondary-myelofibrosis

  Myelofibrosis (MF) is a complex blood disorder characterized by an enlarged spleen, various blood cell abnormalities, and potential complications such as vascular issues and progression to a more aggressive phase. […] Secondary myelofibrosis (SMF) encompasses a range of conditions where the bone marrow’s ability to produce blood cells is restricted, leading to fibrosis. Due to its multiple causes, it occurs more commonly than primary myelofibrosis. […] Secondary Myelofibrosis is a result of previous damage to the bone marrow, for it to be considered secondary, there must be a health history of any of the following conditions: Key genetic mutations like JAK2V617F, CALR, and MPL, Chronic kidney disease, Long-term chemotherapy use, especially drugs that are poisonous to the blood cells, Hemolytic anemias, Abnormal growth of cells or tissues in the body(?), Leukemia, multiple myeloma, or other blood cancers, Cancer cells that have spread throughout the body, Inflammatory processes that have passed like; granulomas, osteomyelitis, autoimmune disorders, etc, Conditions of the bone marrow, like scars from biopsies, dead tissue or radiation, Bone diseases that affect bone replacement and formation.

• #44 Myelofibrosis – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/myelofibrosis

  Myelofibrosis may occur on its own because of certain gene mutations, or it may occur as a result of other blood disorders. […] Primary myelofibrosis is myelofibrosis that develops on its own, due to certain genetic mutations. […] About half of people who have primary myelofibrosis have a mutation in the Janus kinase 2 (JAK2) gene. […] Other people have a mutation in the gene called calreticulin (CALR), which is involved in making proteins that are needed for proper cell function, or in the thrombopoietin receptor gene (MPL), which is involved in cell growth. […] Secondary myelofibrosis occurs as a result of other disorders, particularly other blood disorders such as chronic myeloid leukemia, polycythemia vera, thrombocythemia, multiple myeloma, and lymphoma. […] It may also occur in people with tuberculosis, pulmonary hypertension, systemic lupus erythematosus (lupus), systemic sclerosis, and HIV infection, and in people in whom a cancer has spread to the bones.

• #45 Distinguishing Autoimmune Myelofibrosis from Primary Myelofibrosis – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/september-2018/distinguishing-autoimmune-myelofibrosis-from-primary-myelofibrosis/

  Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF; it can be secondary to a defined autoimmune disease, or it can be primary in the absence of a clinically diagnosed autoimmune disease but the presence of serologic evidence of autoantibodies. […] Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF and is most often accompanied by other autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. When BMF is associated with a defined autoimmune disease, it is termed secondary AIMF. […] It is imperative to differentiate AIMF from PMF because the clinical course, prognostic implication, and treatment options are vastly different. […] Cytokine-dependent mechanisms drive BMF in both AIMF and PMF; however, the predominant source of cytokines—including transforming growth factor beta (TGF-β), interferon gamma (IFN-γ), interleukin 8 (IL-8), IL-2, IL-17, and lipocalin-2 (LCN2)—likely differs, with cytokines derived from lymphoid aggregates driving AIMF and those derived from megakaryocytes and platelets mediating fibrosis in PMF.

• #46 Myelofibrosis – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/myelofibrosis

  Myelofibrosis may occur on its own because of certain gene mutations, or it may occur as a result of other blood disorders. […] Primary myelofibrosis is myelofibrosis that develops on its own, due to certain genetic mutations. […] About half of people who have primary myelofibrosis have a mutation in the Janus kinase 2 (JAK2) gene. […] Other people have a mutation in the gene called calreticulin (CALR), which is involved in making proteins that are needed for proper cell function, or in the thrombopoietin receptor gene (MPL), which is involved in cell growth. […] Secondary myelofibrosis occurs as a result of other disorders, particularly other blood disorders such as chronic myeloid leukemia, polycythemia vera, thrombocythemia, multiple myeloma, and lymphoma. […] It may also occur in people with tuberculosis, pulmonary hypertension, systemic lupus erythematosus (lupus), systemic sclerosis, and HIV infection, and in people in whom a cancer has spread to the bones.

• #47 Myelofibrosis – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/myelofibrosis

  Myelofibrosis may occur on its own because of certain gene mutations, or it may occur as a result of other blood disorders. […] Primary myelofibrosis is myelofibrosis that develops on its own, due to certain genetic mutations. […] About half of people who have primary myelofibrosis have a mutation in the Janus kinase 2 (JAK2) gene. […] Other people have a mutation in the gene called calreticulin (CALR), which is involved in making proteins that are needed for proper cell function, or in the thrombopoietin receptor gene (MPL), which is involved in cell growth. […] Secondary myelofibrosis occurs as a result of other disorders, particularly other blood disorders such as chronic myeloid leukemia, polycythemia vera, thrombocythemia, multiple myeloma, and lymphoma. […] It may also occur in people with tuberculosis, pulmonary hypertension, systemic lupus erythematosus (lupus), systemic sclerosis, and HIV infection, and in people in whom a cancer has spread to the bones.

• #48 What is Secondary Myelofibrosis? – HealthTree for Myelofibrosis

  https://healthtree.org/myelofibrosis/community/articles/what-is-secondary-myelofibrosis

  Myelofibrosis (MF) is a complex blood disorder characterized by an enlarged spleen, various blood cell abnormalities, and potential complications such as vascular issues and progression to a more aggressive phase. […] Secondary myelofibrosis (SMF) encompasses a range of conditions where the bone marrow’s ability to produce blood cells is restricted, leading to fibrosis. Due to its multiple causes, it occurs more commonly than primary myelofibrosis. […] Secondary Myelofibrosis is a result of previous damage to the bone marrow, for it to be considered secondary, there must be a health history of any of the following conditions: Key genetic mutations like JAK2V617F, CALR, and MPL, Chronic kidney disease, Long-term chemotherapy use, especially drugs that are poisonous to the blood cells, Hemolytic anemias, Abnormal growth of cells or tissues in the body(?), Leukemia, multiple myeloma, or other blood cancers, Cancer cells that have spread throughout the body, Inflammatory processes that have passed like; granulomas, osteomyelitis, autoimmune disorders, etc, Conditions of the bone marrow, like scars from biopsies, dead tissue or radiation, Bone diseases that affect bone replacement and formation.

• #49 Distinguishing Autoimmune Myelofibrosis from Primary Myelofibrosis – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/september-2018/distinguishing-autoimmune-myelofibrosis-from-primary-myelofibrosis/

  The presentations are quite different in the 2 entities. Both frequently present with cytopenias; however, patients who have PMF generally present with a much greater symptom burden, including constitutional symptoms, and frequently with debilitating fatigue and diffuse bone pain. […] Clonality is a major distinguishing factor between PMF and AIMF. […] Ultimately, the response to treatment can often aid the clinician in deciphering the underlying cause of BMF. The cytopenias associated with AIMF frequently respond to a brief course of corticosteroids. […] In AIMF, therapy with corticosteroids and other immunosuppressants often results in BMF regression.

• #50 Distinguishing Autoimmune Myelofibrosis from Primary Myelofibrosis – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/september-2018/distinguishing-autoimmune-myelofibrosis-from-primary-myelofibrosis/

  Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF; it can be secondary to a defined autoimmune disease, or it can be primary in the absence of a clinically diagnosed autoimmune disease but the presence of serologic evidence of autoantibodies. […] Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF and is most often accompanied by other autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. When BMF is associated with a defined autoimmune disease, it is termed secondary AIMF. […] It is imperative to differentiate AIMF from PMF because the clinical course, prognostic implication, and treatment options are vastly different. […] Cytokine-dependent mechanisms drive BMF in both AIMF and PMF; however, the predominant source of cytokines—including transforming growth factor beta (TGF-β), interferon gamma (IFN-γ), interleukin 8 (IL-8), IL-2, IL-17, and lipocalin-2 (LCN2)—likely differs, with cytokines derived from lymphoid aggregates driving AIMF and those derived from megakaryocytes and platelets mediating fibrosis in PMF.

• #51 Distinguishing Autoimmune Myelofibrosis from Primary Myelofibrosis – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/september-2018/distinguishing-autoimmune-myelofibrosis-from-primary-myelofibrosis/

  Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF; it can be secondary to a defined autoimmune disease, or it can be primary in the absence of a clinically diagnosed autoimmune disease but the presence of serologic evidence of autoantibodies. […] Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF and is most often accompanied by other autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. When BMF is associated with a defined autoimmune disease, it is termed secondary AIMF. […] It is imperative to differentiate AIMF from PMF because the clinical course, prognostic implication, and treatment options are vastly different. […] Cytokine-dependent mechanisms drive BMF in both AIMF and PMF; however, the predominant source of cytokines—including transforming growth factor beta (TGF-β), interferon gamma (IFN-γ), interleukin 8 (IL-8), IL-2, IL-17, and lipocalin-2 (LCN2)—likely differs, with cytokines derived from lymphoid aggregates driving AIMF and those derived from megakaryocytes and platelets mediating fibrosis in PMF.

• #52 Distinguishing Autoimmune Myelofibrosis from Primary Myelofibrosis – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/september-2018/distinguishing-autoimmune-myelofibrosis-from-primary-myelofibrosis/

  AIMF is a distinct entity characterized by diffuse BMF, with recognizable morphologic and clinical features distinct from those of PMF. More importantly, AIMF is a benign condition with a good prognosis. […] The mechanism by which cytokine release is stimulated in AIMF is not well understood but is believed to be due to aberrant CD8+ lymphocyte activation. […] The second confounding diagnostic factor is the high prevalence of autoimmune phenomena associated with PMF. […] Although the presence of an associated autoimmune disease or serologic evidence of autoantibodies is expected in AIMF, typically documented by a positive antinuclear antibody, rheumatoid factor, or direct antiglobulin test result, none of these serologies is specific to AIMF. […] The relationship between autoimmune diseases and MPNs, however, remains unclear, and a variety of factors is likely involved.

• #53 Distinguishing Autoimmune Myelofibrosis from Primary Myelofibrosis – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/september-2018/distinguishing-autoimmune-myelofibrosis-from-primary-myelofibrosis/

  The presentations are quite different in the 2 entities. Both frequently present with cytopenias; however, patients who have PMF generally present with a much greater symptom burden, including constitutional symptoms, and frequently with debilitating fatigue and diffuse bone pain. […] Clonality is a major distinguishing factor between PMF and AIMF. […] Ultimately, the response to treatment can often aid the clinician in deciphering the underlying cause of BMF. The cytopenias associated with AIMF frequently respond to a brief course of corticosteroids. […] In AIMF, therapy with corticosteroids and other immunosuppressants often results in BMF regression.

• #54 Myelofibrosis | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/myelofibrosis

  Healthcare professionals have discovered some genetic changes in the DNA that can cause myelofibrosis, including changes to the: Janus kinase 2 gene, also called JAK2. Calreticulin gene, also called CALR. Thrombopoietin receptor gene, also called MPL. […] Although the cause of myelofibrosis often isn’t known, healthcare professionals have found some things that might raise the risk. Risk factors include: Another blood cell condition. A small portion of people with myelofibrosis develop the condition as a complication of essential thrombocythemia or polycythemia vera. […] Myelofibrosis has been linked to high levels of exposure to the industrial chemical benzene. […] People exposed to very high doses of radiation have an increased risk of myelofibrosis.

• #55 How Did I Get Myelofibrosis? – HealthTree for Myelofibrosis

  https://healthtree.org/myelofibrosis/community/articles/myelofibrosis-causes

  Myelofibrosis is a rare blood cancer and stem-cell disorder that causes scarring of the bone marrow. Myelo means bone, and fibrosis refers to the development of fibrous scar tissue. […] In myelofibrosis, these stem cells become mutated, although it is not known how these genetic mutations happen. […] No one knows what triggers the start of myelofibrosis. However, researchers have determined that it is not inherited genetically, so it does not run in families. […] Risk factors associated with myelofibrosis include: Age over 65 years (average age of diagnosis is 65 years), Exposure to certain chemicals, such as toluene and benzene, Exposure to very high levels of radiation, Mutation of the Janus kinase 2 (JAK2) gene (50% to 60% of people with myelofibrosis), Mutation of the calreticulin (CALR) gene, Mutation of the myeloproliferative leukemia protein (MPL) gene. […] However, some people with myelofibrosis don’t have any identifiable gene mutations.

• #56 How Did I Get Myelofibrosis? – HealthTree for Myelofibrosis

  https://healthtree.org/myelofibrosis/community/articles/myelofibrosis-causes

  Myelofibrosis is a rare blood cancer and stem-cell disorder that causes scarring of the bone marrow. Myelo means bone, and fibrosis refers to the development of fibrous scar tissue. […] In myelofibrosis, these stem cells become mutated, although it is not known how these genetic mutations happen. […] No one knows what triggers the start of myelofibrosis. However, researchers have determined that it is not inherited genetically, so it does not run in families. […] Risk factors associated with myelofibrosis include: Age over 65 years (average age of diagnosis is 65 years), Exposure to certain chemicals, such as toluene and benzene, Exposure to very high levels of radiation, Mutation of the Janus kinase 2 (JAK2) gene (50% to 60% of people with myelofibrosis), Mutation of the calreticulin (CALR) gene, Mutation of the myeloproliferative leukemia protein (MPL) gene. […] However, some people with myelofibrosis don’t have any identifiable gene mutations.

• #57 What Is Myelofibrosis? Symptoms, Causes, Diagnosis, Treatment, and Prevention

  https://www.everydayhealth.com/leukemia/what-is-myelofibrosis-symptoms-causes-diagnosis-treatment-and-prevention/

  And some people with myelofibrosis don’t have any known gene mutations. […] Potential risk factors include: […] Having another blood cell disorder, such as polycythemia vera (PV) or essential thrombocythemia (ET) […] Exposure to certain industrial chemicals, such as toluene or benzene […] Exposure to ionizing radiation, such as the radiation from X-rays, computerized tomography (CT) scans, positron emission tomography (PET) scans, and radon, a natural radioactive gas found in some homes. […] However, the biggest individual risk factor for blood cancers like myelofibrosis is likely due to aging, Mesa notes. […] Though anyone can develop myelofibrosis, it’s most common in people older than 50.

• #58 FloridaHealthFinder | Myelofibrosis | Health Encyclopedia | FloridaHealthFinder

  https://quality.dev.healthfinder.fl.gov/health-encyclopedia/HIE/1/000531

  Myelofibrosis is a disorder of the bone marrow in which the marrow is replaced by fibrous scar tissue. […] The cause of myelofibrosis is often unknown. There are no known risk factors. When it occurs, it often develops slowly in people over age 50. Women and men are equally affected. There is an increased occurrence of this condition in Ashkenazi Jews. […] Blood and bone marrow cancers, such as myelodysplastic syndrome, leukemia, and lymphoma, may also cause bone marrow scarring. This is called secondary myelofibrosis.

• #59 FloridaHealthFinder | Myelofibrosis | Health Encyclopedia | FloridaHealthFinder

  https://quality.dev.healthfinder.fl.gov/health-encyclopedia/HIE/1/000531

  Myelofibrosis is a disorder of the bone marrow in which the marrow is replaced by fibrous scar tissue. […] The cause of myelofibrosis is often unknown. There are no known risk factors. When it occurs, it often develops slowly in people over age 50. Women and men are equally affected. There is an increased occurrence of this condition in Ashkenazi Jews. […] Blood and bone marrow cancers, such as myelodysplastic syndrome, leukemia, and lymphoma, may also cause bone marrow scarring. This is called secondary myelofibrosis.

• #60 Idiopathic Myelofibrosis: Symptoms, Causes, and Diagnosis

  https://nhoreviveresearch.com/blogs/guide-about-idiopathic-myelofibrosis/

  Idiopathic myelofibrosis is often referred to as primary myelofibrosis when it develops on its own without an underlying cause. However, it can also develop secondary to other conditions, leading to a key distinction between primary vs idiopathic myelofibrosis. […] Talking about the causes, as the term idiopathic implies, the causes are unknown. However, certain genetic mutations are known to be the background reason for the diseases onset. […] These mutations, particularly in the JAK2, CALR, and MPL genes, cause the bone marrow to produce blood cells abnormally. These genetic mutations do not guarantee the development of idiopathic myelofibrosis, but they are a significant risk factor. Additionally, exposure to certain toxins or radiation has been suggested as a contributing factor in some cases, though these are fewer common causes.

• #61 Myelofibrosis (MF) – MPN Voice

  https://www.mpnvoice.org.uk/about-mpns/questions/myelofibrosis-mf/

  Myelofibrosis (MF) is a blood cancer which affects the way blood cells are produced in the body. […] Recent research shows that about 50-60% of people with MF have a mutation (or change) in a protein called JAK2, a protein that regulates blood cell production. A further 30% of patients have mutations in a gene called calreticulin referred to as CALR, between 5-10% of patients have mutations in the platelet hormone receptor called MPL. Other mutations in many genes are found in patients with MF but these are also seen in blood diseases. […] Patients with MF are not born with these mutations but acquire them during their lives. It is also important to note that MF is rarely inherited and is not passed on from parent to child, although some families do seem to develop the disease more readily than others. […] We are learning more but additional research needs to be done to determine the causes of MF.

• #62 What is myelofibrosis? | Blood Cancer UK

  https://bloodcancer.org.uk/understanding-blood-cancer/myelofibrosis/what-is-myelofibrosis/

  Myelofibrosis (MF) is caused by specific genetic changes that happen during someone’s lifetime although we don’t know why. […] About a third of people with MF previously had another MPN either ET or PV which has developed into MF.

• #63 Primary myelofibrosis – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/myeloproliferative-neoplasms/primary-myelofibrosis/

  Primary myelofibrosis is a rare chronic disorder diagnosed in an estimated 1 per 100,000 population. It can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years. The cause of primary myelofibrosis remains largely unknown. […] Long-term exposure to high levels of benzene or very high doses of ionising radiation may increase the risk of primary myelofibrosis in a small number of cases. Around one third of people with myelofibrosis have been previously diagnosed with polycythaemia (post-polycythaemic myelofibrosis) or essential thrombocythaemia (post-ET myelofibrosis). […] A mutation in JAK2 is found in about 50% of people with primary myelofibrosis. It is unclear at present why some patients with mutations in JAK2 develop myelofibrosis and others don’t.

• #64 What is Secondary Myelofibrosis? – HealthTree for Myelofibrosis

  https://healthtree.org/myelofibrosis/community/articles/what-is-secondary-myelofibrosis

  Myelofibrosis (MF) is a complex blood disorder characterized by an enlarged spleen, various blood cell abnormalities, and potential complications such as vascular issues and progression to a more aggressive phase. […] Secondary myelofibrosis (SMF) encompasses a range of conditions where the bone marrow’s ability to produce blood cells is restricted, leading to fibrosis. Due to its multiple causes, it occurs more commonly than primary myelofibrosis. […] Secondary Myelofibrosis is a result of previous damage to the bone marrow, for it to be considered secondary, there must be a health history of any of the following conditions: Key genetic mutations like JAK2V617F, CALR, and MPL, Chronic kidney disease, Long-term chemotherapy use, especially drugs that are poisonous to the blood cells, Hemolytic anemias, Abnormal growth of cells or tissues in the body(?), Leukemia, multiple myeloma, or other blood cancers, Cancer cells that have spread throughout the body, Inflammatory processes that have passed like; granulomas, osteomyelitis, autoimmune disorders, etc, Conditions of the bone marrow, like scars from biopsies, dead tissue or radiation, Bone diseases that affect bone replacement and formation.

• #65 Myelofibrosis | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/myelofibrosis

  Healthcare professionals have discovered some genetic changes in the DNA that can cause myelofibrosis, including changes to the: Janus kinase 2 gene, also called JAK2. Calreticulin gene, also called CALR. Thrombopoietin receptor gene, also called MPL. […] Although the cause of myelofibrosis often isn’t known, healthcare professionals have found some things that might raise the risk. Risk factors include: Another blood cell condition. A small portion of people with myelofibrosis develop the condition as a complication of essential thrombocythemia or polycythemia vera. […] Myelofibrosis has been linked to high levels of exposure to the industrial chemical benzene. […] People exposed to very high doses of radiation have an increased risk of myelofibrosis.

• #66 Myelofibrosis: Symptoms, Types, Prognosis & Treatment

  https://my.clevelandclinic.org/health/diseases/15672-myelofibrosis

  Myelofibrosis is a rare type of blood cancer where your bone marrow (the soft, spongy tissue inside of your bones) is replaced by fibrous scar tissue. […] With myelofibrosis, a change (mutation) in a stem cells DNA causes the cell to become defective, or a cancer cell, instead. The cell multiplies, passing the mutation onto new cells. […] Scientists dont know what causes myelofibrosis, but they know its associated with DNA changes in specific genes. […] About 60% to 65 % of people with myelofibrosis have a mutation in the JAK2 gene. Another 5% to 10% have a mutation in the myeloproliferative leukemia (MPL) gene. A mutation called calreticulin (CALR) accounts for approximately 20% to 25 % of myelofibrosis cases. […] Youre at increased risk of myelofibrosis if: […] You have primary thrombocytosis or polycythemia vera. […] Youve been exposed to ionizing radiation or petrochemicals like benzene or toluene.

• #67 Myelofibrosis – MPN Research Foundation

  https://mpnresearchfoundation.org/primary-myelofibrosis-pmf/

  Researchers believe MF may be caused by abnormal blood stem cells in the bone marrow. […] Recently, researchers have discovered that these diseases may be caused by acquired gene mutations (changes in DNA that not inherited). […] Risk factors associated with MF include: […] Exposure to petrochemicals (e.g., benzene and toluene) and ionizing radiation may increase the risk of developing MF. […] Approximately 50% to 60% of people with MF have a mutation of the JAK2 gene within their blood-forming cells. […] About 23.5% of people with myelofibrosis and essential thrombocythemia have a mutation called Calreticulin, or CALR.

• #68 Myelofibrosis | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/myelofibrosis

  Healthcare professionals have discovered some genetic changes in the DNA that can cause myelofibrosis, including changes to the: Janus kinase 2 gene, also called JAK2. Calreticulin gene, also called CALR. Thrombopoietin receptor gene, also called MPL. […] Although the cause of myelofibrosis often isn’t known, healthcare professionals have found some things that might raise the risk. Risk factors include: Another blood cell condition. A small portion of people with myelofibrosis develop the condition as a complication of essential thrombocythemia or polycythemia vera. […] Myelofibrosis has been linked to high levels of exposure to the industrial chemical benzene. […] People exposed to very high doses of radiation have an increased risk of myelofibrosis.

• #69 Pathogenetic mechanisms in primary myelofibrosis – UpToDate

  https://www.uptodate.com/contents/pathogenetic-mechanisms-in-primary-myelofibrosis/print

  The occurrence of PMF has, in a minority of cases, been linked to exposure to thorium dioxide, petroleum manufacturing plants (especially toluene and benzene), and ionizing radiation. […] A very high incidence of PMF has been noted in patients given thorium-based radiographic contrast material and in individuals exposed to atomic bombs at Hiroshima.

• #70 Myelofibrosis- Meaning, Treatment Available, Causes & More

  https://www.impactguru.com/info/myelofibrosis/

  Some evidence suggests that exposure to high levels of ionizing radiation may increase the risk of developing this rare disease. […] Prolonged exposure to some chemicals, like benzene, has been linked to an increased risk of getting myelofibrosis. […] Chronic inflammation may contribute to the development of myelofibrosis. […] In some cases, the cause of myelofibrosis remains unknown. There may be a combination of genetic environmental factors that contribute to the development of the disease.

• #71 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. […] Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. […] The exact pathogenesis of MF is not fully understood. However, better understanding of the role of increased JAK-STAT signaling [either through activating mutations (JAK2V617F, MPL515L/K) within the signaling pathway, or mutations involving CALR], the role of deregulated pro-inflammatory cytokine expression, and the impaired bone marrow microenvironment is transforming the treatment approach for MF. […] A major biological hallmark of MF is a significant elevation in circulating pro-inflammatory cytokines.

• #72 Primary Myelofibrosis Diagnosis & Disease Information

  https://www.cancertherapyadvisor.com/ddi/primary-myelofibrosis/

  The cause of primary myelofibrosis is multifactorial. Genetic mutations are the primary driver of abnormal blood cell production. The most frequently identified mutation in primary myelofibrosis is the Janus kinase 2 (JAK2) V617F mutation, which is found in approximately 43% to 57% of patients with primary myelofibrosis. This mutation causes constant activation of the JAK/signal transducer and activator of transcription (JAK-STAT) signaling pathway, which leads to increased production of myeloid cells. In addition, CALR gene mutations are involved in disease pathogenesis in 25% to 30% of cases, whereas MPL gene mutations are found in 5% of patients with primary myelofibrosis. Altogether, these mutations affect normal signaling, which is required for blood cell formation, and cause fibrotic change in the bone marrow. […] Causes of death in patients with primary myelofibrosis include progression to leukemia, cardiovascular events, infections, and bleeding.

• #73 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #74 Primary Myelofibrosis Diagnosis & Disease Information

  https://www.cancertherapyadvisor.com/ddi/primary-myelofibrosis/

  The cause of primary myelofibrosis is multifactorial. Genetic mutations are the primary driver of abnormal blood cell production. The most frequently identified mutation in primary myelofibrosis is the Janus kinase 2 (JAK2) V617F mutation, which is found in approximately 43% to 57% of patients with primary myelofibrosis. This mutation causes constant activation of the JAK/signal transducer and activator of transcription (JAK-STAT) signaling pathway, which leads to increased production of myeloid cells. In addition, CALR gene mutations are involved in disease pathogenesis in 25% to 30% of cases, whereas MPL gene mutations are found in 5% of patients with primary myelofibrosis. Altogether, these mutations affect normal signaling, which is required for blood cell formation, and cause fibrotic change in the bone marrow. […] Causes of death in patients with primary myelofibrosis include progression to leukemia, cardiovascular events, infections, and bleeding.

• #75 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #76 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #77 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #78 Primary myelofibrosis – Wikipedia

  https://en.wikipedia.org/wiki/Primary_myelofibrosis

  Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL genes. […] The underlying cause of PMF is almost always related to an acquired mutation in JAK2, CALR or MPL in a hematopoietic stem/progenitor cell in the bone marrow. There is an association between mutations to the JAK2, CALR, or MPL genes and myelofibrosis. Approximately 90% of those with myelofibrosis have one of these mutations; 10% do not have mutations in these three genes. […] The JAK2 protein is mutated giving risk to a variant protein with an amino acid substitution commonly referred to as V617F; the mutation causing this variant is found in approximately half of individuals with primary myelofibrosis. […] The MPL gene codes for a protein that acts as a receptor for thrombopoietin, a growth factor that enhances production of platelets. A mutation in that gene, resulting in the substitution W515L, results in thrombopoietin receptor that is constitutively active even in the absence of thrompoietin.

• #79 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #80 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. […] Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. […] The exact pathogenesis of MF is not fully understood. However, better understanding of the role of increased JAK-STAT signaling [either through activating mutations (JAK2V617F, MPL515L/K) within the signaling pathway, or mutations involving CALR], the role of deregulated pro-inflammatory cytokine expression, and the impaired bone marrow microenvironment is transforming the treatment approach for MF. […] A major biological hallmark of MF is a significant elevation in circulating pro-inflammatory cytokines.

• #81 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #82 Primary myelofibrosis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/primary-myelofibrosis?lang=us

  Primary myelofibrosis is a myeloproliferative neoplasm in which the bone marrow is replaced with collagenous connective tissue resulting in progressive fibrosis. […] It is a chronic clonal stem cell disorder of neoplastic megakaryocytes and is considered a BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homologue 1)-negative myeloproliferative disorder. […] Progressive bone marrow fibrosis is the result of collagen produced by non-neoplastic fibroblasts in response to inappropriate release of PDGF and TGF- from the neoplastic megakaryocytes.

• #83 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Megakaryocytes and platelets form the central arm in myelofibrosis. […] At each of these steps different cytokines, vitamins, hormones and minerals interact to produce the fibrocollagenous matrix. […] Many signals converge to produce TGF- that stimulates marrow fibrosis. […] The major fibrogenic factor, TGF-, is a multifunctional growth factor that is mostly produced by megakaryocytes and platelets in the marrow. TGF- can also be independently produced by metastatic and infiltrating cells of immune origin to stimulate marrow fibrosis. […] Fibrogenic stimuli may originate from neoplastic or nonneoplastic cells that release specific factors such as growth factors, cytokines and chemokines. This leads to proliferation of selective immunophenotype bearing mesenchymal stem cell populations that differentiate to myofibroblasts and fibroblasts that initiate fibrosis.

• #84 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #85 Distinguishing Autoimmune Myelofibrosis from Primary Myelofibrosis – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/september-2018/distinguishing-autoimmune-myelofibrosis-from-primary-myelofibrosis/

  Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF; it can be secondary to a defined autoimmune disease, or it can be primary in the absence of a clinically diagnosed autoimmune disease but the presence of serologic evidence of autoantibodies. […] Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF and is most often accompanied by other autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. When BMF is associated with a defined autoimmune disease, it is termed secondary AIMF. […] It is imperative to differentiate AIMF from PMF because the clinical course, prognostic implication, and treatment options are vastly different. […] Cytokine-dependent mechanisms drive BMF in both AIMF and PMF; however, the predominant source of cytokines—including transforming growth factor beta (TGF-β), interferon gamma (IFN-γ), interleukin 8 (IL-8), IL-2, IL-17, and lipocalin-2 (LCN2)—likely differs, with cytokines derived from lymphoid aggregates driving AIMF and those derived from megakaryocytes and platelets mediating fibrosis in PMF.

• #86 Distinguishing Autoimmune Myelofibrosis from Primary Myelofibrosis – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/september-2018/distinguishing-autoimmune-myelofibrosis-from-primary-myelofibrosis/

  Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF; it can be secondary to a defined autoimmune disease, or it can be primary in the absence of a clinically diagnosed autoimmune disease but the presence of serologic evidence of autoantibodies. […] Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF and is most often accompanied by other autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. When BMF is associated with a defined autoimmune disease, it is termed secondary AIMF. […] It is imperative to differentiate AIMF from PMF because the clinical course, prognostic implication, and treatment options are vastly different. […] Cytokine-dependent mechanisms drive BMF in both AIMF and PMF; however, the predominant source of cytokines—including transforming growth factor beta (TGF-β), interferon gamma (IFN-γ), interleukin 8 (IL-8), IL-2, IL-17, and lipocalin-2 (LCN2)—likely differs, with cytokines derived from lymphoid aggregates driving AIMF and those derived from megakaryocytes and platelets mediating fibrosis in PMF.

• #87 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #88 Pathogenetic mechanisms in primary myelofibrosis – UpToDate

  https://www.uptodate.com/contents/pathogenetic-mechanisms-in-primary-myelofibrosis/print

  Primary myelofibrosis (PMF, chronic idiopathic myelofibrosis, agnogenic myeloid metaplasia) is one of the chronic myeloproliferative neoplasms, which are collectively characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. […] The primary disease process in PMF is a clonal hematopoietic stem cell disorder that results in chronic myeloproliferation and atypical megakaryocytic hyperplasia. […] The exact cause of primary myelofibrosis (PMF) is unknown. PMF, along with the other chronic myeloproliferative disorders, chronic myeloid leukemia, polycythemia vera, and essential thrombocythemia, is considered to arise from a somatic mutation of a pluripotent hematopoietic progenitor cell. […] A defective stem cell „niche” within the bone marrow has been postulated for PMF.

• #89 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #90 Pathogenetic mechanisms in primary myelofibrosis – UpToDate

  https://www.uptodate.com/contents/pathogenetic-mechanisms-in-primary-myelofibrosis/print

  Primary myelofibrosis (PMF, chronic idiopathic myelofibrosis, agnogenic myeloid metaplasia) is one of the chronic myeloproliferative neoplasms, which are collectively characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. […] The primary disease process in PMF is a clonal hematopoietic stem cell disorder that results in chronic myeloproliferation and atypical megakaryocytic hyperplasia. […] The exact cause of primary myelofibrosis (PMF) is unknown. PMF, along with the other chronic myeloproliferative disorders, chronic myeloid leukemia, polycythemia vera, and essential thrombocythemia, is considered to arise from a somatic mutation of a pluripotent hematopoietic progenitor cell. […] A defective stem cell „niche” within the bone marrow has been postulated for PMF.

• #91 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The MF inflammatory cytokine signature is believed to be both a consequence of the malignant clone as well an integral modifier of the bone marrow microenvironment, thereby, promoting malignant hematopoiesis. […] Several other studies of MF found increases in various inflammatory cytokines. […] Some studies have demonstrated dysregulation in the levels of various other circulating cytokines, although the findings have not been reproducible in all studies. […] The expanded osteoblastic lineage cells have increased expression of genes involved in the regulation of extracellular matrix, cell adhesion, and inflammatory responses. […] JAK2V617F is constitutively active resulting in chronic activation of the JAK-STAT pathway. […] The exact mechanism by which JAK2V617F contributes to the pathogenesis of MF is not fully known.

• #92 Myelofibrosis: Causes and Treatments

  https://www.drkarunhematology.com/blog/myelofibrosis-causes-and-treatments/

  Myelofibrosis originates from the malfunctioning of stem cells in the bone marrow. […] While the exact cause of myelofibrosis remains unclear, several factors contribute to its development. Knowing these underlying causes can aid in early detection and management of the condition. Here they are: […] Certain genetic mutations, such as JAK2, CALR, and MPL mutations, are associated with the development of myelofibrosis. […] Pre-existing bone marrow disorders, such as polycythemia vera or essential thrombocythemia, can progress to myelofibrosis. […] Dysregulated immune responses, including aberrant T-cell activation and cytokine signalling, can also play a role in the pathogenesis of myelofibrosis. […] Aberrant epigenetic changes involving DNA methylation and histone modifications contribute to the dysregulation of gene expression in myelofibrosis.

• #93 Myelofibrosis: Causes and Treatments

  https://www.drkarunhematology.com/blog/myelofibrosis-causes-and-treatments/

  Myelofibrosis originates from the malfunctioning of stem cells in the bone marrow. […] While the exact cause of myelofibrosis remains unclear, several factors contribute to its development. Knowing these underlying causes can aid in early detection and management of the condition. Here they are: […] Certain genetic mutations, such as JAK2, CALR, and MPL mutations, are associated with the development of myelofibrosis. […] Pre-existing bone marrow disorders, such as polycythemia vera or essential thrombocythemia, can progress to myelofibrosis. […] Dysregulated immune responses, including aberrant T-cell activation and cytokine signalling, can also play a role in the pathogenesis of myelofibrosis. […] Aberrant epigenetic changes involving DNA methylation and histone modifications contribute to the dysregulation of gene expression in myelofibrosis.

• #94 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. […] It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. […] Fibrosis of the marrow is always secondary to a primary event which may be clonal or non clonal.

• #95 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. […] It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. […] Fibrosis of the marrow is always secondary to a primary event which may be clonal or non clonal.

• #96 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Megakaryocytes and platelets form the central arm in myelofibrosis. […] At each of these steps different cytokines, vitamins, hormones and minerals interact to produce the fibrocollagenous matrix. […] Many signals converge to produce TGF- that stimulates marrow fibrosis. […] The major fibrogenic factor, TGF-, is a multifunctional growth factor that is mostly produced by megakaryocytes and platelets in the marrow. TGF- can also be independently produced by metastatic and infiltrating cells of immune origin to stimulate marrow fibrosis. […] Fibrogenic stimuli may originate from neoplastic or nonneoplastic cells that release specific factors such as growth factors, cytokines and chemokines. This leads to proliferation of selective immunophenotype bearing mesenchymal stem cell populations that differentiate to myofibroblasts and fibroblasts that initiate fibrosis.

• #97 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. […] It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. […] Fibrosis of the marrow is always secondary to a primary event which may be clonal or non clonal.

• #98 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Megakaryocytes and platelets form the central arm in myelofibrosis. […] At each of these steps different cytokines, vitamins, hormones and minerals interact to produce the fibrocollagenous matrix. […] Many signals converge to produce TGF- that stimulates marrow fibrosis. […] The major fibrogenic factor, TGF-, is a multifunctional growth factor that is mostly produced by megakaryocytes and platelets in the marrow. TGF- can also be independently produced by metastatic and infiltrating cells of immune origin to stimulate marrow fibrosis. […] Fibrogenic stimuli may originate from neoplastic or nonneoplastic cells that release specific factors such as growth factors, cytokines and chemokines. This leads to proliferation of selective immunophenotype bearing mesenchymal stem cell populations that differentiate to myofibroblasts and fibroblasts that initiate fibrosis.

• #99 What is Secondary Myelofibrosis? – HealthTree for Myelofibrosis

  https://healthtree.org/myelofibrosis/community/articles/what-is-secondary-myelofibrosis

  Myelofibrosis is caused when fibroblasts (cells that create scar tissue) grow in the bone marrow, interfering with the blood supply and replacing blood-forming cells with inactive fibrous tissue. So, anything that can cause fibrous tissue to form in the bone marrow can potentially induce secondary myelofibrosis.

• #100 Primary myelofibrosis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/primary-myelofibrosis?lang=us

  Primary myelofibrosis is a myeloproliferative neoplasm in which the bone marrow is replaced with collagenous connective tissue resulting in progressive fibrosis. […] It is a chronic clonal stem cell disorder of neoplastic megakaryocytes and is considered a BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homologue 1)-negative myeloproliferative disorder. […] Progressive bone marrow fibrosis is the result of collagen produced by non-neoplastic fibroblasts in response to inappropriate release of PDGF and TGF- from the neoplastic megakaryocytes.

• #101 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  Targeting fibrogenic cytokine expression either alone or in combination with a JAK2 inhibitor is an active area of research in MF. […] The potential impact of KB004 on BMF in responding patients is of interest. […] BMF is seen in many hematologic and non-hematologic conditions and is a prominent pathologic feature of MF. […] BMF is a culminating effect of a complex interplay between MPN cells and supporting stromal cells through the interaction of various inflammatory cytokines such as TGF-.

• #102 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. […] It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. […] Fibrosis of the marrow is always secondary to a primary event which may be clonal or non clonal.

• #103 Myelofibrosis | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/myelofibrosis

  Myelofibrosis sometimes happens on its own. This is called primary myelofibrosis. Sometimes it’s caused by another blood cell condition. When this happens, it’s called secondary myelofibrosis. […] It’s often not clear what causes myelofibrosis. This cancer happens in the bone marrow. Bone marrow is the soft matter inside the bones where blood cells are made. […] Myelofibrosis starts when blood stem cells in the bone marrow develop changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. In healthy blood stem cells, the DNA gives instructions to turn into blood cells in a controlled way. […] In myelofibrosis, the DNA changes give different instructions to the blood stem cells. The changes tell the blood stem cells to make more blood cells than the body needs. The blood cells don’t work like healthy blood cells.

• #104 Myelofibrosis: Symptoms, Types, Prognosis & Treatment

  https://my.clevelandclinic.org/health/diseases/15672-myelofibrosis

  Myelofibrosis is a rare type of blood cancer where your bone marrow (the soft, spongy tissue inside of your bones) is replaced by fibrous scar tissue. […] With myelofibrosis, a change (mutation) in a stem cells DNA causes the cell to become defective, or a cancer cell, instead. The cell multiplies, passing the mutation onto new cells. […] Scientists dont know what causes myelofibrosis, but they know its associated with DNA changes in specific genes. […] About 60% to 65 % of people with myelofibrosis have a mutation in the JAK2 gene. Another 5% to 10% have a mutation in the myeloproliferative leukemia (MPL) gene. A mutation called calreticulin (CALR) accounts for approximately 20% to 25 % of myelofibrosis cases. […] Youre at increased risk of myelofibrosis if: […] You have primary thrombocytosis or polycythemia vera. […] Youve been exposed to ionizing radiation or petrochemicals like benzene or toluene.

• #105 Myelofibrosis – Blood Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/blood-disorders/myeloproliferative-disorders/myelofibrosis

  Myelofibrosis may occur on its own because of certain gene mutations, or it may occur as a result of other blood disorders. […] Primary myelofibrosis is myelofibrosis that develops on its own, due to certain genetic mutations. […] About half of people who have primary myelofibrosis have a mutation in the Janus kinase 2 (JAK2) gene. […] Other people have a mutation in the gene called calreticulin (CALR), which is involved in making proteins that are needed for proper cell function, or in the thrombopoietin receptor gene (MPL), which is involved in cell growth. […] Secondary myelofibrosis occurs as a result of other disorders, particularly other blood disorders such as chronic myeloid leukemia, polycythemia vera, thrombocythemia, multiple myeloma, and lymphoma. […] It may also occur in people with tuberculosis, pulmonary hypertension, systemic lupus erythematosus (lupus), systemic sclerosis, and HIV infection, and in people in whom a cancer has spread to the bones.

• #106 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  Targeting fibrogenic cytokine expression either alone or in combination with a JAK2 inhibitor is an active area of research in MF. […] The potential impact of KB004 on BMF in responding patients is of interest. […] BMF is seen in many hematologic and non-hematologic conditions and is a prominent pathologic feature of MF. […] BMF is a culminating effect of a complex interplay between MPN cells and supporting stromal cells through the interaction of various inflammatory cytokines such as TGF-.

• #107 Fibrosis and bone marrow: understanding causation and pathobiology | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04393-z

  Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. […] It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. […] Fibrosis of the marrow is always secondary to a primary event which may be clonal or non clonal.

• #108 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  The regression of BMF after HSCT was associated with a better overall survival. […] The goals of MF-directed treatment can be divided into two broad categories: clonal eradication and treatments targeting various signaling pathways and mediators implicated in BMF. […] However, there are several published reports describing reversibility of BMF with interferon- (IFN-) based therapy. […] With the introduction of selective JAK2 inhibitors into clinical investigation over the last 10 years, initial expectation of clonal suppression as measured by elimination of molecular and karyotypic abnormalities was dampened by the observations of persistent clonal hematopoiesis and unaltered MPN bone marrow pathological features. […] Ruxolitinib-treated patients who achieved stabilization or improvement in grade of BMF at 24 months had a reduced relative risk of death in this analysis.

• #109 Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5013940/

  Targeting fibrogenic cytokine expression either alone or in combination with a JAK2 inhibitor is an active area of research in MF. […] The potential impact of KB004 on BMF in responding patients is of interest. […] BMF is seen in many hematologic and non-hematologic conditions and is a prominent pathologic feature of MF. […] BMF is a culminating effect of a complex interplay between MPN cells and supporting stromal cells through the interaction of various inflammatory cytokines such as TGF-.

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