Materiały źródłowe

• #1 Waldenstrom’s Macroglobulinemia | CancerIndex

  http://www.cancerindex.org/clinks4y.htm

  This is a rare malignant condition, involving an excess of beta-lymphocytes (a type of cell in the immune system) which secrete immunoglobulins (a type of antibody). […] The Waldenstrom’s Macroglobulinemia program at Dana Farber Cancer Institute (DFCI) was founded in 1999 by Dr. Steve Treon with the help of patients, caregivers and DFCI scientists in an effort to advance understanding of the cause of WM, and to pursue novel therapies. […] Waldenstrm macroglobulinemia (WM) is a rare, indolent B-cell lymphoma. […] The MYD88 L265P mutation is present in nearly 90% of patients with Waldenstrm macroglobulinemia. […] Familial clustering of Waldenstrm macroglobulinemia (WM) has been observed for nearly 6 decades. […] The initial evaluation of the patient with Waldenstrm macroglobulinemia can be challenging.

• #2 Orphanet: Waldenström macroglobulinemia

  https://www.orpha.net/en/disease/detail/33226

  A rare indolent B-cell non-Hodgkin lymphoma, characterized by the infiltration of monoclonal lymphoplasmacytic cells in the bone marrow and the production of serum immunoglobulin M (IgM) monoclonal protein. […] Exact etiology is unknown. Familial predisposition has been described in around 20-30% of WM cases, and first-degree relatives of WM patients have an increased risk of developing the disease. The most important acquired risk factor is preexisting IgM-MGUS.

• #3 Etiology of Waldenström Macroglobulinemia: Genetic Factors and Immune-related Conditions

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7243894/

  Epidemiologic studies provide an insight into the etiology of lymphoplasmacytic lymphoma/Waldenstrm macroglobulinemia, which indicates that repetitive immune stimulation and genetic factors play an important role. […] Although the etiology of WM remains to be better clarified, analysis of emerging data suggests that there may be a link between the immune system and genetic factors that are involved in the development of WM. […] Taken as a whole, our outcomes provide further evidence that supported the hypothesis that chronic stimulation of the immune system is linked to the etiology of WM. […] Familial clustering of LPL/WM is well documented and has been published in case-control cohort studies and multiply affected families. […] Our results expand on previous studies that suggest that there is a role for shared common susceptibility genes that predispose to LPL/WM and certain lymphoproliferative disorders.

• #4 What Causes Waldenström’s Macroglobulinemia: Genetic or Immune-Related Factors, or a Combination?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7020666/

  Population-based studies suggest a role for chronic immune stimulation and genetic factors in the causation of lymphoplasmacytic lymphoma (LPL)/Waldenstrms macroglobulinemia (WM). […] Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors and genetic in the etiology of LPL/WM, which will be reviewed in this paper. […] Taken together, our results support that chronic immune stimulation plays a role in the pathogenesis of LPL/WM. […] Our findings that both personal and family history of Sjgrens syndrome or autoimmune hemolytic anemia were associated with increased risk of LPL/WM indicate that there might be some shared (genetic, environmental, or both) susceptibility for these conditions. […] Together with previous studies, our findings support a role for shared common susceptibility genes that predispose to LPL/WM and certain lymphoproliferative disorders. […] There are a number of gene candidates that could be causing susceptibility to LPL/WM and related conditions. […] Emerging data support a role for germline susceptibility genes in the causation of LPL/WM and other lymphoproliferative disorders.

• #5 Waldenström macroglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/Waldenstr%C3%B6m_macroglobulinemia

  Waldenstrm macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes. The most commonly associated mutations, based on whole-genome sequencing of 30 patients, are a somatic mutation in MYD88 (90% of patients) and a somatic mutation in CXCR4 (27% of patients). CXCR4 mutations cause symptomatic hyperviscosity syndrome and high bone marrow activity characteristic of the disease. However, CXCR4 mutation is not associated with splenomegaly, high platelet counts, or different response to therapy, questioning the relevance of CXCR4 in treating patients. An association has been demonstrated with the locus 6p21.3 on chromosome 6. […] There are genetic factors with first-degree relatives of Waldenstrm macroglobulinemia patients shown to have a highly increased risk of also developing the disease. There is also evidence to suggest that environmental factors, including exposure to farming, pesticides, wood dust, and organic solvents, may influence the development of Waldenstrm macroglobulinemia.

• #6 Waldenstrom Macroglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207097-overview

  No definite etiology exists for Waldenstrm macroglobulinemia. Environmental, familial, genetic, and viral factors have been reported. IgM monoclonal gammopathies of undetermined significance (MGUS) are considered a precursor of Waldenstrm macroglobulinemia. […] A possible role for genetic factors has been suggested by reports of familial clustering of Waldenstrm macroglobulinemia. In one study, approximately 20% of 181 serial Waldenstrm macroglobulinemia patients presenting to a tertiary referral had a first-degree relative with either Waldenstrm macroglobulinemia or another B-cell lymphoproliferative disease. Reports of familial cases suggest a genetic predisposition. […] The MYD88 L265P somatic mutation, in which leucine is replaced by proline at position 265, is found in white blood cells in approximately 90% of Waldenstrm macroglobulinemia cases. The mutation results in overactivity of the altered MyD88 protein, stimulating the signaling molecules that activate nuclear factor-kappa-B; this may protect lymphoplasmacytic cells against apoptosis.

• #7 Waldenström Macroglobulinemia: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17951-waldenstrom-macroglobulinemia

  Waldenstrm macroglobulinemia causes genetic mutations cause Waldenstrm macroglobulinemia. More than 90% of people (9 out of 10) with WM have a mutation involving the MYD88 gene. And about 40% (4 out of 10) have changes to their CXCR4 gene. Both mutations help the abnormal cells in Waldenstrm macroglobulinemia multiply. […] These changes arent inherited (hereditary). This means you cant pass this on to your children, and you didnt get it from your parents. Instead, they develop during your lifetime. But researchers dont know what triggers the mutations in the first place.

• #8 What Causes Waldenstrom Macroglobulinemia? | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/what-causes.html

  Recent research has found that about 9 times out of 10, WM cells have a mutation (change) in a gene known as MYD88, which normally helps immune system cells signal each other and helps keep them alive. The DNA change in this gene might make it stay turned on all the time, which might help the WM cells survive longer than they should. […] Researchers have found that some patients with WM have important changes or defects in other bone marrow cells. These changes might also help cancer cells grow. Certain cells in the bone marrow called dendritic cells release a hormone called interleukin-6 (IL-6) that helps normal plasma cells and plasmacytoid lymphocytes grow. Excess IL-6 production by these cells appears to be an important factor in the development of WM. […] Scientists are learning about the exact gene changes that cause WM. But even though they have found some of these gene changes, they still do not know why these changes occur.

• #9 Frequently Asked Questions – Waldenstrom’s Macroglobulinemia – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/frequently-asked-questions-waldenstrom-macroglobulinemia/

  Several studies have suggested that people with WM can get any type of cancer, but they have an increased risk of acute myeloid leukemia (AML), diffuse large B cell lymphoma, melanoma, other skin cancers, and thyroid cancer. […] Its significance is still not understood. Although it is prevalent in WM (approximately 90% of patients), at this point we do not believe it causes the disease. However, it does appear to play a role in the proliferation and survival of WM cells by leading to over-expression of proteins such as BTK that are involved in B-cell development and activation. […] Researchers are looking at several other gene mutations found in WM patients. Such work is still preliminary, but at least one mutation in the gene CXCR4 is found in approximately 30-40% of WM patients.

• #10 Waldenström macroglobulinemia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia/

  Waldenström macroglobulinemia is a rare blood cell cancer characterized by an excess of abnormal white blood cells in the bone marrow. […] It is not clear what causes Waldenström macroglobulinemia, though it is likely to result from a combination of genetic changes. The most common known genetic change associated with this condition is a variant (also called mutation) in the MYD88 gene, which is found in more than 90 percent of affected individuals. Another gene commonly associated with Waldenström macroglobulinemia, CXCR4, is altered in approximately 30 percent of affected individuals (most of whom also have the MYD88 gene variant). […] Variants in these genes lead to production of proteins that are constantly turned on (overactive). Excessive signaling through these overactive proteins allows survival and proliferation of abnormal cells that should undergo apoptosis, which likely contributes to the accumulation of lymphoplasmacytic cells in Waldenström macroglobulinemia. […] The variants that cause Waldenström macroglobulinemia are acquired during a person’s lifetime and are present only in the abnormal blood cells.

• #11 Waldenstrom Macroglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207097-overview

  Less common somatic genetic changes that have been found in Waldenstrm macroglobulinemia include variants in ARID1A, which have been associated with increased disease burden, and variants in MLL2. Other MYD88 mutations have also been found. Somatic activating mutations in the C-terminal domain of the C-X-C chemokine receptor type 4 (CXCR4) gene have been found in 20% to 40% of patients. […] Hepatitis C, hepatitis G, and human herpesvirus 8 have been implicated, but as yet, no strong data support a causative link between these viruses and Waldenstrm macroglobulinemia.

• #12 Waldenstrom Macroglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207097-overview

  No definite etiology exists for Waldenstrm macroglobulinemia. Environmental, familial, genetic, and viral factors have been reported. IgM monoclonal gammopathies of undetermined significance (MGUS) are considered a precursor of Waldenstrm macroglobulinemia. […] A possible role for genetic factors has been suggested by reports of familial clustering of Waldenstrm macroglobulinemia. In one study, approximately 20% of 181 serial Waldenstrm macroglobulinemia patients presenting to a tertiary referral had a first-degree relative with either Waldenstrm macroglobulinemia or another B-cell lymphoproliferative disease. Reports of familial cases suggest a genetic predisposition. […] The MYD88 L265P somatic mutation, in which leucine is replaced by proline at position 265, is found in white blood cells in approximately 90% of Waldenstrm macroglobulinemia cases. The mutation results in overactivity of the altered MyD88 protein, stimulating the signaling molecules that activate nuclear factor-kappa-B; this may protect lymphoplasmacytic cells against apoptosis.

• #13 Waldenström macroglobulinemia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia/

  Waldenström macroglobulinemia is a rare blood cell cancer characterized by an excess of abnormal white blood cells in the bone marrow. […] It is not clear what causes Waldenström macroglobulinemia, though it is likely to result from a combination of genetic changes. The most common known genetic change associated with this condition is a variant (also called mutation) in the MYD88 gene, which is found in more than 90 percent of affected individuals. Another gene commonly associated with Waldenström macroglobulinemia, CXCR4, is altered in approximately 30 percent of affected individuals (most of whom also have the MYD88 gene variant). […] Variants in these genes lead to production of proteins that are constantly turned on (overactive). Excessive signaling through these overactive proteins allows survival and proliferation of abnormal cells that should undergo apoptosis, which likely contributes to the accumulation of lymphoplasmacytic cells in Waldenström macroglobulinemia. […] The variants that cause Waldenström macroglobulinemia are acquired during a person’s lifetime and are present only in the abnormal blood cells.

• #14 Waldenström Macroglobulinemia – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/january-2015/waldenstrom-macroglobulinemia/

  Waldenströms macroglobulinemia (WM) is an indolent low-grade lymphoma characterized by bone marrow infiltration with lymphoplasmacytic cells associated with a monoclonal immunoglobulin M protein. It is considered incurable. […] Insights into mutations in MYD88 L265P and the WHIM-like CXCR4 have been shown to be significant not just in terms of their diagnostic and prognostic value, but also as potential targets for therapy. […] Somatic mutations in MYD88 L265P and the WHIM-like CXCR4 are common findings in patients with WM and have implications for the pathogenesis and outcome of patients with WM. MYD88 mutations are seen in more than 90% of patients with WM, and CXCR4 mutations are seen in up to 30% of patients. […] The cytogenetic abnormalities and somatic mutations reported in patients with WM are outlined in Table 2. Other gene polymorphisms of predictive potential include the expression of the hCNT1 gene. […] Newer biological insights into MYD88 and WHIM-like CXCR4 have been significant and intriguing not just in terms of their diagnostic and prognostic value, but also as potential targets for therapy in patients with WM.

• #15 Waldenström macroglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/Waldenstr%C3%B6m_macroglobulinemia

  Waldenstrm macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes. The most commonly associated mutations, based on whole-genome sequencing of 30 patients, are a somatic mutation in MYD88 (90% of patients) and a somatic mutation in CXCR4 (27% of patients). CXCR4 mutations cause symptomatic hyperviscosity syndrome and high bone marrow activity characteristic of the disease. However, CXCR4 mutation is not associated with splenomegaly, high platelet counts, or different response to therapy, questioning the relevance of CXCR4 in treating patients. An association has been demonstrated with the locus 6p21.3 on chromosome 6. […] There are genetic factors with first-degree relatives of Waldenstrm macroglobulinemia patients shown to have a highly increased risk of also developing the disease. There is also evidence to suggest that environmental factors, including exposure to farming, pesticides, wood dust, and organic solvents, may influence the development of Waldenstrm macroglobulinemia.

• #16 Waldenström macroglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/Waldenstr%C3%B6m_macroglobulinemia

  Waldenstrm macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes. The most commonly associated mutations, based on whole-genome sequencing of 30 patients, are a somatic mutation in MYD88 (90% of patients) and a somatic mutation in CXCR4 (27% of patients). CXCR4 mutations cause symptomatic hyperviscosity syndrome and high bone marrow activity characteristic of the disease. However, CXCR4 mutation is not associated with splenomegaly, high platelet counts, or different response to therapy, questioning the relevance of CXCR4 in treating patients. An association has been demonstrated with the locus 6p21.3 on chromosome 6. […] There are genetic factors with first-degree relatives of Waldenstrm macroglobulinemia patients shown to have a highly increased risk of also developing the disease. There is also evidence to suggest that environmental factors, including exposure to farming, pesticides, wood dust, and organic solvents, may influence the development of Waldenstrm macroglobulinemia.

• #17 Waldenstrom’s Macroglobulinemia: Causes, Symptoms, and Treatment

  https://www.webmd.com/cancer/lymphoma/waldenstrom-macroglobulinemia-overview

  Experts think that changes in your DNA may lead to the disease. Nine out of 10 times, Waldenstrom’s macroglobulinemia cells have a change on a gene called MYD88. Researchers have also linked another gene, CXCR4, to the disease. […] Scientists are studying what causes these DNA changes. They know that they aren’t passed down from your parents. Most of the time, the changes happen later in life. This may explain why Waldenstrom’s macroglobulinemia is usually diagnosed in older people. […] The disease is more common in men than women. Your chances of having Waldenstrom’s macroglobulinemia are higher if you: Are 50 or older, Are white, Have a condition called MGUS (monoclonal gammopathy of undetermined significance), Have a relative with a disease that affects their white blood cells.

• #18 What Causes Waldenstrom Macroglobulinemia? | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/what-causes.html

  Some risk factors can make a person more likely to get Waldenstrom macroglobulinemia (WM), but often its not clear exactly how these factors might increase risk. […] Scientists have learned how certain changes in the DNA inside normal lymphocytes can make them become lymphoma or multiple myeloma cells. Changes in the DNA of some lymphoma cells can also cause them to make high levels of IgM, which leads to most of the symptoms of WM. […] Some people inherit DNA changes from a parent that increase their risk for certain types of cancer. Researchers are studying families that have many cases of WM to try to find the genes that might cause this disorder in some people. […] The DNA changes found in WM cells are usually acquired after birth (not passed on from a parent). Some of these acquired changes may have outside causes, but often they occur for no apparent reason. They seem to happen more often as we age, which might help explain why WM usually occurs in older people.

• #19 Waldenström’s Macroglobulinemia | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/waldenstroms-macroglobulinemia

  Waldenstrm’s macroglobulinemia (WM) is an uncommon blood cell cancer that originates from malignant B-cells. It is a slow-growing type of non-Hodgkin lymphoma. […] The disease occurs because of an abnormality in B lymphocytes in the bone marrow, causing them to produce too much immunoglobulin protein (IgM) that thickens the blood. […] Up to 20% of WM patients have a first- or second-degree relative with WM or another lymphoma, multiple myeloma, or chronic lymphocytic leukemia. This suggests there may be a genetic risk factor. […] Our colleagues in the Center for Early Detection and Interception of Blood Cancers are studying the genetic and epigenetic factors that characterize conditions that are often precancerous to WM, such as smoldering Waldenstrm’s macroglobulinemia and Monoclonal Gammopathy of Undetermined Significance (MGUS). […] We are credited with discovering the MYD88 and CXCR4 mutations in WM, the approval of the first-ever drug for WM (ibrutinib), and advancing many new drugs through clinical trials.

• #20 Waldenstrom Macroglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207097-overview

  No definite etiology exists for Waldenstrm macroglobulinemia. Environmental, familial, genetic, and viral factors have been reported. IgM monoclonal gammopathies of undetermined significance (MGUS) are considered a precursor of Waldenstrm macroglobulinemia. […] A possible role for genetic factors has been suggested by reports of familial clustering of Waldenstrm macroglobulinemia. In one study, approximately 20% of 181 serial Waldenstrm macroglobulinemia patients presenting to a tertiary referral had a first-degree relative with either Waldenstrm macroglobulinemia or another B-cell lymphoproliferative disease. Reports of familial cases suggest a genetic predisposition. […] The MYD88 L265P somatic mutation, in which leucine is replaced by proline at position 265, is found in white blood cells in approximately 90% of Waldenstrm macroglobulinemia cases. The mutation results in overactivity of the altered MyD88 protein, stimulating the signaling molecules that activate nuclear factor-kappa-B; this may protect lymphoplasmacytic cells against apoptosis.

• #21 Frequently Asked Questions – Waldenstrom’s Macroglobulinemia – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/frequently-asked-questions-waldenstrom-macroglobulinemia/

  What risk factors cause WM? Is there an environmental cause? […] The specific cause(s) of WM are unknown. Male sex, Caucasian race, increasing age, a family history of WM or other B cell disorders, hepatitis C virus infection, AIDS infection, occupations such as farming, and exposure to pesticides, solvents, and wood dust are possible risk factors for the disease. More studies are needed to determine if there is a causal relationship between any of these factors and WM. […] WM is preceded by a condition known as monoclonal gammopathy of undetermined significance (MGUS) of the IgM type and is the very early stage when there are very few WM cells in the bone marrow. […] There is a slightly increased familial predisposition to WM, with most studies suggesting that up to 25% of people with WM have a history of the disease or related B cell disorders in their families.

• #22 Etiology of Waldenström Macroglobulinemia: Genetic Factors and Immune-related Conditions

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7243894/

  A few potential candidate genes may underlie familial LPL/WM and related conditions. […] Very recently, Treon et al, by using tumor cell (somatic) DNA extracted from LPL cells in the bone marrow, performed whole-genome sequencing on 54 patients with WM and found that 91% of these patients had a recurrent somatic mutation in chromosome 3 that corresponded to MYD88 L265P, a gene that encodes an adapter molecule involved in signal transduction in innate immunity. […] There is emerging evidence that supports a role for germ line genetic polymorphisms, somatic mutations, and even environmental factors (ie, a personal history of exposure to certain infectious diseases) to be intrinsically linked to the etiology of LPL/WM and other lymphoproliferative disorders.

• #23 What Causes Waldenstrom Macroglobulinemia? | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/what-causes.html

  Some risk factors can make a person more likely to get Waldenstrom macroglobulinemia (WM), but often its not clear exactly how these factors might increase risk. […] Scientists have learned how certain changes in the DNA inside normal lymphocytes can make them become lymphoma or multiple myeloma cells. Changes in the DNA of some lymphoma cells can also cause them to make high levels of IgM, which leads to most of the symptoms of WM. […] Some people inherit DNA changes from a parent that increase their risk for certain types of cancer. Researchers are studying families that have many cases of WM to try to find the genes that might cause this disorder in some people. […] The DNA changes found in WM cells are usually acquired after birth (not passed on from a parent). Some of these acquired changes may have outside causes, but often they occur for no apparent reason. They seem to happen more often as we age, which might help explain why WM usually occurs in older people.

• #24 What Causes Waldenström’s Macroglobulinemia: Genetic or Immune-Related Factors, or a Combination?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7020666/

  Population-based studies suggest a role for chronic immune stimulation and genetic factors in the causation of lymphoplasmacytic lymphoma (LPL)/Waldenstrms macroglobulinemia (WM). […] Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors and genetic in the etiology of LPL/WM, which will be reviewed in this paper. […] Taken together, our results support that chronic immune stimulation plays a role in the pathogenesis of LPL/WM. […] Our findings that both personal and family history of Sjgrens syndrome or autoimmune hemolytic anemia were associated with increased risk of LPL/WM indicate that there might be some shared (genetic, environmental, or both) susceptibility for these conditions. […] Together with previous studies, our findings support a role for shared common susceptibility genes that predispose to LPL/WM and certain lymphoproliferative disorders. […] There are a number of gene candidates that could be causing susceptibility to LPL/WM and related conditions. […] Emerging data support a role for germline susceptibility genes in the causation of LPL/WM and other lymphoproliferative disorders.

• #25 Risk Factors for Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/risk-factors.html

  Some studies have found that people with chronic hepatitis C infection might be more likely to develop WM than people without the virus. But not all studies have found such a link. […] Some research has suggested that people with certain types of autoimmune disease, such as Sjgren (Sjogren) syndrome, might be at higher risk for WM.

• #26 What Causes Waldenström’s Macroglobulinemia: Genetic or Immune-Related Factors, or a Combination?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7020666/

  Population-based studies suggest a role for chronic immune stimulation and genetic factors in the causation of lymphoplasmacytic lymphoma (LPL)/Waldenstrms macroglobulinemia (WM). […] Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors and genetic in the etiology of LPL/WM, which will be reviewed in this paper. […] Taken together, our results support that chronic immune stimulation plays a role in the pathogenesis of LPL/WM. […] Our findings that both personal and family history of Sjgrens syndrome or autoimmune hemolytic anemia were associated with increased risk of LPL/WM indicate that there might be some shared (genetic, environmental, or both) susceptibility for these conditions. […] Together with previous studies, our findings support a role for shared common susceptibility genes that predispose to LPL/WM and certain lymphoproliferative disorders. […] There are a number of gene candidates that could be causing susceptibility to LPL/WM and related conditions. […] Emerging data support a role for germline susceptibility genes in the causation of LPL/WM and other lymphoproliferative disorders.

• #27 Risk Factors for Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/risk-factors.html

  Some studies have found that people with chronic hepatitis C infection might be more likely to develop WM than people without the virus. But not all studies have found such a link. […] Some research has suggested that people with certain types of autoimmune disease, such as Sjgren (Sjogren) syndrome, might be at higher risk for WM.

• #28 Waldenstrom Macroglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207097-overview

  Less common somatic genetic changes that have been found in Waldenstrm macroglobulinemia include variants in ARID1A, which have been associated with increased disease burden, and variants in MLL2. Other MYD88 mutations have also been found. Somatic activating mutations in the C-terminal domain of the C-X-C chemokine receptor type 4 (CXCR4) gene have been found in 20% to 40% of patients. […] Hepatitis C, hepatitis G, and human herpesvirus 8 have been implicated, but as yet, no strong data support a causative link between these viruses and Waldenstrm macroglobulinemia.

• #29 What Causes Waldenstrom Macroglobulinemia? | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/what-causes.html

  Recent research has found that about 9 times out of 10, WM cells have a mutation (change) in a gene known as MYD88, which normally helps immune system cells signal each other and helps keep them alive. The DNA change in this gene might make it stay turned on all the time, which might help the WM cells survive longer than they should. […] Researchers have found that some patients with WM have important changes or defects in other bone marrow cells. These changes might also help cancer cells grow. Certain cells in the bone marrow called dendritic cells release a hormone called interleukin-6 (IL-6) that helps normal plasma cells and plasmacytoid lymphocytes grow. Excess IL-6 production by these cells appears to be an important factor in the development of WM. […] Scientists are learning about the exact gene changes that cause WM. But even though they have found some of these gene changes, they still do not know why these changes occur.

• #30 What Causes Waldenström’s Macroglobulinemia: Genetic or Immune-Related Factors, or a Combination?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7020666/

  Population-based studies suggest a role for chronic immune stimulation and genetic factors in the causation of lymphoplasmacytic lymphoma (LPL)/Waldenstrms macroglobulinemia (WM). […] Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors and genetic in the etiology of LPL/WM, which will be reviewed in this paper. […] Taken together, our results support that chronic immune stimulation plays a role in the pathogenesis of LPL/WM. […] Our findings that both personal and family history of Sjgrens syndrome or autoimmune hemolytic anemia were associated with increased risk of LPL/WM indicate that there might be some shared (genetic, environmental, or both) susceptibility for these conditions. […] Together with previous studies, our findings support a role for shared common susceptibility genes that predispose to LPL/WM and certain lymphoproliferative disorders. […] There are a number of gene candidates that could be causing susceptibility to LPL/WM and related conditions. […] Emerging data support a role for germline susceptibility genes in the causation of LPL/WM and other lymphoproliferative disorders.

• #31 Risk Factors for Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/risk-factors.html

  Monoclonal gammopathy of undetermined significance (MGUS) is an abnormality of antibody-making cells that is related to multiple myeloma and WM. […] Researchers have found a few risk factors that make a person more likely to develop Waldenstrom macroglobulinemia (WM). But most people with these risk factors never develop WM. […] The risk of WM goes up with age. It is rare among people younger than 50 years old. […] WM is more common among White people than among African Americans. In contrast, multiple myeloma is about twice as common among African Americans as White Americans. The reasons for these differences are not known. […] Men are more likely than women to develop this disease. The reason for this is not known. […] Inherited genes seem to play a role in at least some people who get WM. About 1 in 5 people with WM has a close relative with WM or with a related B-cell disease, such as MGUS or certain types of lymphoma or leukemia.

• #32 Risk Factors for Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/risk-factors.html

  Monoclonal gammopathy of undetermined significance (MGUS) is an abnormality of antibody-making cells that is related to multiple myeloma and WM. […] Researchers have found a few risk factors that make a person more likely to develop Waldenstrom macroglobulinemia (WM). But most people with these risk factors never develop WM. […] The risk of WM goes up with age. It is rare among people younger than 50 years old. […] WM is more common among White people than among African Americans. In contrast, multiple myeloma is about twice as common among African Americans as White Americans. The reasons for these differences are not known. […] Men are more likely than women to develop this disease. The reason for this is not known. […] Inherited genes seem to play a role in at least some people who get WM. About 1 in 5 people with WM has a close relative with WM or with a related B-cell disease, such as MGUS or certain types of lymphoma or leukemia.

• #33 Bing Center for Waldenstrom’s Macroglobulinemia – About Waldenstrom’s Macroglobulinemia

  http://waldenstroms.com/about-wm

  Waldenströms macroglobulinemia (WM) is an uncommon blood cell cancer that originates from malignant B-cells. It is a slow-growing type of non-Hodgkin lymphoma. Waldenströms mostly forms in the bone marrow and can slow the growth of normal blood cells, which can lead to anemia and a weakened immune system. […] The disease stems from an abnormality in B lymphocytes in the bone marrow, causing them to overproduce an immunoglobulin protein (IgM) that thickens the blood. […] Up to 20% of WM patients have a first or second degree relative with WM or another lymphoma, myeloma or chronic lymphocytic leukemia suggesting a familial predisposition. […] The genetic basis for familial or ethnic WM is unknown, and research studies are underway at our center in collaboration with the National Institutes of Health to identify genetic basis for predisposition. […] The chance of developing Waldenströms increases with age; the average age at which someone is diagnosed is their mid-60s.

• #34 Risk Factors for Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/risk-factors.html

  Monoclonal gammopathy of undetermined significance (MGUS) is an abnormality of antibody-making cells that is related to multiple myeloma and WM. […] Researchers have found a few risk factors that make a person more likely to develop Waldenstrom macroglobulinemia (WM). But most people with these risk factors never develop WM. […] The risk of WM goes up with age. It is rare among people younger than 50 years old. […] WM is more common among White people than among African Americans. In contrast, multiple myeloma is about twice as common among African Americans as White Americans. The reasons for these differences are not known. […] Men are more likely than women to develop this disease. The reason for this is not known. […] Inherited genes seem to play a role in at least some people who get WM. About 1 in 5 people with WM has a close relative with WM or with a related B-cell disease, such as MGUS or certain types of lymphoma or leukemia.

• #35

  https://www.janssenwithme.com/en/blood-cancer/waldenstroms-macroglobulinemia

  Waldenstrm’s Macroglobulinaemia (WM) is a rare type of cancer that affects your white blood cells. Its also known to be a slow-growing form of Non-Hodgkins Lymphoma. […] Unfortunately, the cause for WM is still unknown, but research has been able to highlight some uncontrollable factors that can influence the development of the disease: Gender: more common in men, Age: 60 years and older, Race: Caucasians are more likely to develop WM.

• #36 Risk Factors for Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/risk-factors.html

  Monoclonal gammopathy of undetermined significance (MGUS) is an abnormality of antibody-making cells that is related to multiple myeloma and WM. […] Researchers have found a few risk factors that make a person more likely to develop Waldenstrom macroglobulinemia (WM). But most people with these risk factors never develop WM. […] The risk of WM goes up with age. It is rare among people younger than 50 years old. […] WM is more common among White people than among African Americans. In contrast, multiple myeloma is about twice as common among African Americans as White Americans. The reasons for these differences are not known. […] Men are more likely than women to develop this disease. The reason for this is not known. […] Inherited genes seem to play a role in at least some people who get WM. About 1 in 5 people with WM has a close relative with WM or with a related B-cell disease, such as MGUS or certain types of lymphoma or leukemia.

• #37 What is Waldenström macroglobulinaemia (WM)? | Blood Cancer UK

  https://bloodcancer.org.uk/understanding-blood-cancer/lymphoma/waldenstrom-macroglobulinaemia/what-is-wm/

  Waldenstrm macroglobulinaemia (WM) happens when blood cells called plasma cells develop in an unusual way in your bone marrow. […] WM is very rare. Around 350 people are diagnosed with WM in the UK each year. Theres no clear cause of WM, but certain factors can affect how likely you are to develop it: […] You’re more likely to develop the condition if you have a relative with WM, although this is very rare. Your risk may also be higher if you have a family history of autoimmune conditions (where your body mistakenly attacks healthy cells, such as Sjgren syndrome), or certain infectious diseases. […] People from a white European background tend to have a higher risk of developing WM.

• #38 Facts About Waldenström Macroglobulinemia | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/diseases/waldenstrom-macroglobulinemia/facts-resources.html

  Waldenstrm macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is one type of cancer of the lymph system. […] The exact cause of WM is unknown. You may be at higher risk if any of these is true: […] You have a blood disorder called monoclonal gammopathy of undetermined significance (MGUS). About 1 to 2 percent of people with MGUS will develop a related cancer, like WM, lymphoma or multiple myeloma or another serious condition, like amyloidosis. […] You have a family history of the condition. About 1 in 5 people with WM has a close relative with WM or a related B-cell disease. […] You have hepatitis C. Some, but not all, studies show infection with the hepatitis C virus raises WM risk. […] You have certain autoimmune diseases, such as Sjgren syndrome, which might increase risk. […] Keep in mind that many people who get the disease have none of these risk factors, and most people with these risk factors do not develop the disease.

• #39 What Causes Waldenström Macroglobulinemia and How Will It Affect Me? – The Waiting Room

  https://thewaitingroom.karger.com/tell-me-about/what-causes-waldenstrom-macroglobulinemia-and-how-will-it-affect-me/

  Most people develop a condition called IgM monoclonal gammopathy of uncertain significance (IgM MGUS) before WM. […] IgM MGUS becomes more common as people get older, but its cause is unknown. […] Over time (usually years), the monoclonal LPL cells may build up to result in WM, which is eventually diagnosed once symptoms develop, such as fatigue, weight loss, sweats, fevers, nerve damage (peripheral neuropathy) or infections (due to an under-functioning immune system). […] WM is not infectious and cannot be passed on to other people. But blood relatives in the persons immediate family are slightly more likely to develop WM or another kind of B-cell lymphoma. […] Most people with WM (about 90%) have a mutation in the MYD88 gene in the DNA of the LPL cells. […] About 40% of patients with WM have a mutation in the CXCR4 gene, which affects production of a different protein. […] These gene mutations result in abnormal proteins that do not work properly in the bodys cells. […] Everyone who is suspected of having WM ideally should be tested for these gene mutations, as they may affect treatment choices.

• #40 Waldenström macroglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/Waldenstr%C3%B6m_macroglobulinemia

  Waldenstrm macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes. The most commonly associated mutations, based on whole-genome sequencing of 30 patients, are a somatic mutation in MYD88 (90% of patients) and a somatic mutation in CXCR4 (27% of patients). CXCR4 mutations cause symptomatic hyperviscosity syndrome and high bone marrow activity characteristic of the disease. However, CXCR4 mutation is not associated with splenomegaly, high platelet counts, or different response to therapy, questioning the relevance of CXCR4 in treating patients. An association has been demonstrated with the locus 6p21.3 on chromosome 6. […] There are genetic factors with first-degree relatives of Waldenstrm macroglobulinemia patients shown to have a highly increased risk of also developing the disease. There is also evidence to suggest that environmental factors, including exposure to farming, pesticides, wood dust, and organic solvents, may influence the development of Waldenstrm macroglobulinemia.

• #41 Frequently Asked Questions – Waldenstrom’s Macroglobulinemia – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/frequently-asked-questions-waldenstrom-macroglobulinemia/

  What risk factors cause WM? Is there an environmental cause? […] The specific cause(s) of WM are unknown. Male sex, Caucasian race, increasing age, a family history of WM or other B cell disorders, hepatitis C virus infection, AIDS infection, occupations such as farming, and exposure to pesticides, solvents, and wood dust are possible risk factors for the disease. More studies are needed to determine if there is a causal relationship between any of these factors and WM. […] WM is preceded by a condition known as monoclonal gammopathy of undetermined significance (MGUS) of the IgM type and is the very early stage when there are very few WM cells in the bone marrow. […] There is a slightly increased familial predisposition to WM, with most studies suggesting that up to 25% of people with WM have a history of the disease or related B cell disorders in their families.

• #42 Frequently Asked Questions – Waldenstrom’s Macroglobulinemia – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/frequently-asked-questions-waldenstrom-macroglobulinemia/

  What risk factors cause WM? Is there an environmental cause? […] The specific cause(s) of WM are unknown. Male sex, Caucasian race, increasing age, a family history of WM or other B cell disorders, hepatitis C virus infection, AIDS infection, occupations such as farming, and exposure to pesticides, solvents, and wood dust are possible risk factors for the disease. More studies are needed to determine if there is a causal relationship between any of these factors and WM. […] WM is preceded by a condition known as monoclonal gammopathy of undetermined significance (MGUS) of the IgM type and is the very early stage when there are very few WM cells in the bone marrow. […] There is a slightly increased familial predisposition to WM, with most studies suggesting that up to 25% of people with WM have a history of the disease or related B cell disorders in their families.

• #43 Waldenström macroglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/Waldenstr%C3%B6m_macroglobulinemia

  Waldenstrm macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes. The most commonly associated mutations, based on whole-genome sequencing of 30 patients, are a somatic mutation in MYD88 (90% of patients) and a somatic mutation in CXCR4 (27% of patients). CXCR4 mutations cause symptomatic hyperviscosity syndrome and high bone marrow activity characteristic of the disease. However, CXCR4 mutation is not associated with splenomegaly, high platelet counts, or different response to therapy, questioning the relevance of CXCR4 in treating patients. An association has been demonstrated with the locus 6p21.3 on chromosome 6. […] There are genetic factors with first-degree relatives of Waldenstrm macroglobulinemia patients shown to have a highly increased risk of also developing the disease. There is also evidence to suggest that environmental factors, including exposure to farming, pesticides, wood dust, and organic solvents, may influence the development of Waldenstrm macroglobulinemia.

• #44 What Is Waldenström Macroglobulinemia? – The Waiting Room

  https://thewaitingroom.karger.com/tell-me-about/what-is-waldenstrom-macroglobulinemia/

  Waldenstrm macroglobulinemia (shortened to WM) is a rare blood cancer. […] WM develops when a genetic change happens in a B cell as it is developing into a plasma cell. The change or mutation causes the cell to multiply in an uncontrolled way. The abnormal cells carrying the mutation are LPL cells. […] Understanding what causes WM and how the disease develops will help you to ask the right questions and make good treatment choices.

• #45 Waldenstrom Macroglobulinemia | Condition | UAMS Health

  https://uamshealth.com/condition/waldenstrom-macroglobulinemia/

  Waldenstroms cells frequently have a mutation in a gene (genes are comprised of DNA) known as MYD88, which normally helps immune system cells signal each other and helps keep them alive. It is possible that the DNA change in this gene might make it stay turned on all the time, helping the Waldenstroms cells survive longer than they should.

• #46 What Causes Waldenstrom Macroglobulinemia? | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/causes-risks-prevention/what-causes.html

  Recent research has found that about 9 times out of 10, WM cells have a mutation (change) in a gene known as MYD88, which normally helps immune system cells signal each other and helps keep them alive. The DNA change in this gene might make it stay turned on all the time, which might help the WM cells survive longer than they should. […] Researchers have found that some patients with WM have important changes or defects in other bone marrow cells. These changes might also help cancer cells grow. Certain cells in the bone marrow called dendritic cells release a hormone called interleukin-6 (IL-6) that helps normal plasma cells and plasmacytoid lymphocytes grow. Excess IL-6 production by these cells appears to be an important factor in the development of WM. […] Scientists are learning about the exact gene changes that cause WM. But even though they have found some of these gene changes, they still do not know why these changes occur.

• #47 What Causes Waldenström Macroglobulinemia and How Will It Affect Me? – The Waiting Room

  https://thewaitingroom.karger.com/tell-me-about/what-causes-waldenstrom-macroglobulinemia-and-how-will-it-affect-me/

  Most people develop a condition called IgM monoclonal gammopathy of uncertain significance (IgM MGUS) before WM. […] IgM MGUS becomes more common as people get older, but its cause is unknown. […] Over time (usually years), the monoclonal LPL cells may build up to result in WM, which is eventually diagnosed once symptoms develop, such as fatigue, weight loss, sweats, fevers, nerve damage (peripheral neuropathy) or infections (due to an under-functioning immune system). […] WM is not infectious and cannot be passed on to other people. But blood relatives in the persons immediate family are slightly more likely to develop WM or another kind of B-cell lymphoma. […] Most people with WM (about 90%) have a mutation in the MYD88 gene in the DNA of the LPL cells. […] About 40% of patients with WM have a mutation in the CXCR4 gene, which affects production of a different protein. […] These gene mutations result in abnormal proteins that do not work properly in the bodys cells. […] Everyone who is suspected of having WM ideally should be tested for these gene mutations, as they may affect treatment choices.

• #48 Waldenström macroglobulinemia | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/waldenstrom-macroglobulinaemia?lang=us

  Waldenstrm macroglobulinemia is classified as a subtype of lymphoplasmacytic lymphoma with any level of an IgM paraprotein; these two conditions are not synonymous. […] The pathogenesis is poorly understood but may resemble that of chronic lymphocytic leukemia. Clonal proliferation of functionally impaired B-cells occurs, as well as infiltration of various tissues (predominantly bone marrow, spleen, and lymph nodes). There is an overproduction of IgM, leading to hyperviscosity syndrome and resultant impaired microcirculation.

• #49 Pathophysiology and Treatments of Complications of Waldenström’s Macroglobulinemia | Published in Clinical Hematology International

  https://chi.scholasticahq.com/article/124268-pathophysiology-and-treatments-of-complications-of-waldenstrom-s-macroglobulinemia

  Waldenstroms macroglobulinemia (WM) or lymphoplasmacytic lymphoma is a B-cell malignancy characterized by lymphoplasmacytic cells in the bone marrow that secrete high amounts of immunoglobulin (Ig) M. The large pentameric structure of IgM leads to a variety of unique complications in WM, such as hyperviscosity syndrome, cryoglobulinemia and sensory neuropathy. […] The pathophysiology of these complications is mostly related to the pentameric structure of the IgM being produced by LPCs, and include amyloidosis, autoimmune hemolytic anemia, renal disease, increased risk of bleeding, neuropathy and organomegaly. […] IgM molecules can also behave uniquely at low temperatures and aggregate to form even larger molecules called cryoglobulins. Because of the increased density resulting from aggregation, cryoglobulins can precipitate out as large, solid immune complexes in the serum.

• #50 Pathophysiology and Treatments of Complications of Waldenström’s Macroglobulinemia | Published in Clinical Hematology International

  https://chi.scholasticahq.com/article/124268-pathophysiology-and-treatments-of-complications-of-waldenstrom-s-macroglobulinemia

  Waldenstroms macroglobulinemia (WM) or lymphoplasmacytic lymphoma is a B-cell malignancy characterized by lymphoplasmacytic cells in the bone marrow that secrete high amounts of immunoglobulin (Ig) M. The large pentameric structure of IgM leads to a variety of unique complications in WM, such as hyperviscosity syndrome, cryoglobulinemia and sensory neuropathy. […] The pathophysiology of these complications is mostly related to the pentameric structure of the IgM being produced by LPCs, and include amyloidosis, autoimmune hemolytic anemia, renal disease, increased risk of bleeding, neuropathy and organomegaly. […] IgM molecules can also behave uniquely at low temperatures and aggregate to form even larger molecules called cryoglobulins. Because of the increased density resulting from aggregation, cryoglobulins can precipitate out as large, solid immune complexes in the serum.

• #51 Waldenstrom macroglobulinemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/waldenstrom-macroglobulinemia/symptoms-causes/syc-20359967

  Waldenstrom macroglobulinemia (mak-roe-glob-u-lih-NEE-me-uh) is a type of cancer that begins in the white blood cells. […] In Waldenstrom macroglobulinemia, the changes happen in the white blood cells. The changes turn some of the white blood cells into cancer cells. It’s not clear what causes the changes. […] Waldenstrom macroglobulinemia cells make a protein that the body can’t use. The protein is immunoglobulin M, which is also called IgM. IgM can build up in the blood. This may reduce blood flow in the body and cause other problems.

• #52 Waldenström macroglobulinemia | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/waldenstrom-macroglobulinaemia?lang=us

  Waldenstrm macroglobulinemia is classified as a subtype of lymphoplasmacytic lymphoma with any level of an IgM paraprotein; these two conditions are not synonymous. […] The pathogenesis is poorly understood but may resemble that of chronic lymphocytic leukemia. Clonal proliferation of functionally impaired B-cells occurs, as well as infiltration of various tissues (predominantly bone marrow, spleen, and lymph nodes). There is an overproduction of IgM, leading to hyperviscosity syndrome and resultant impaired microcirculation.

• #53 Pathophysiology and Treatments of Complications of Waldenström’s Macroglobulinemia | Published in Clinical Hematology International

  https://chi.scholasticahq.com/article/124268-pathophysiology-and-treatments-of-complications-of-waldenstrom-s-macroglobulinemia

  In WM, we predominantly see type I cryoglobulinemia, which is characterized by cryoglobulins composed of a monoclonal Ig, usually IgM. Sometimes, WM can produce a type II cryoglobulinemia, which is usually composed of a mixture of monoclonal IgM and a rheumatoid factor. […] Neurological complications of WM can occur due to a variety of mechanisms involving IgM and LPCs. In fact, 60% of patients with an IgM monoclonal gammopathy may develop a sensorimotor polyneuropathy. […] Another neurological complication occurs when LPCs extravasate and infiltrate the CNS, in what is known as Bing Neel Syndrome (BNS). The LPCs can induce nerve demyelination, axonal degeneration, and overall CNS degradation. This is a rare complication and only occurs in up to 1% of patients with WM.

• #54

  https://step2.medbullets.com/oncology/422785/waldenstrom-macroglobulinemia

  B-cell lymphoproliferative neoplasm leading to excess production of monoclonal immunoglobulin (IgM) protein […] secondary to lymphoplasmacytic cell infiltration in the bone marrow. […] Etiology […] excessive proliferation of IgM-producing plasmacytoid lymphocytes, leading to the overproduction of abnormal IgM antibodies […] autoantibody attack against myelin-associated glycoprotein […] results in neuropathy. […] IgM against the patient’s red blood cells […] Coombs-positive autoimmune cold hemolytic anemia. […] IgM deposition in the kidneys, gastrointestinal tract, or skin […] leads to serum hyperviscosity […] secondary to IgM’s pentameric configuration. […] Malignant B cells may infiltrate hematopoietic tissues leading to […] cytopenias […] lymphadenopathy […] hepatomegaly […] splenomegaly. […] Genetics […] inheritance pattern […] somatic mutation. […] Mutations […] MDY88 gene. […] Associated conditions […] anemia. […] Epidemiology […] elderly patients […] Caucasian males.

• #55

  https://step2.medbullets.com/oncology/422785/waldenstrom-macroglobulinemia

  B-cell lymphoproliferative neoplasm leading to excess production of monoclonal immunoglobulin (IgM) protein […] secondary to lymphoplasmacytic cell infiltration in the bone marrow. […] Etiology […] excessive proliferation of IgM-producing plasmacytoid lymphocytes, leading to the overproduction of abnormal IgM antibodies […] autoantibody attack against myelin-associated glycoprotein […] results in neuropathy. […] IgM against the patient’s red blood cells […] Coombs-positive autoimmune cold hemolytic anemia. […] IgM deposition in the kidneys, gastrointestinal tract, or skin […] leads to serum hyperviscosity […] secondary to IgM’s pentameric configuration. […] Malignant B cells may infiltrate hematopoietic tissues leading to […] cytopenias […] lymphadenopathy […] hepatomegaly […] splenomegaly. […] Genetics […] inheritance pattern […] somatic mutation. […] Mutations […] MDY88 gene. […] Associated conditions […] anemia. […] Epidemiology […] elderly patients […] Caucasian males.

• #56

  https://step2.medbullets.com/oncology/422785/waldenstrom-macroglobulinemia

  B-cell lymphoproliferative neoplasm leading to excess production of monoclonal immunoglobulin (IgM) protein […] secondary to lymphoplasmacytic cell infiltration in the bone marrow. […] Etiology […] excessive proliferation of IgM-producing plasmacytoid lymphocytes, leading to the overproduction of abnormal IgM antibodies […] autoantibody attack against myelin-associated glycoprotein […] results in neuropathy. […] IgM against the patient’s red blood cells […] Coombs-positive autoimmune cold hemolytic anemia. […] IgM deposition in the kidneys, gastrointestinal tract, or skin […] leads to serum hyperviscosity […] secondary to IgM’s pentameric configuration. […] Malignant B cells may infiltrate hematopoietic tissues leading to […] cytopenias […] lymphadenopathy […] hepatomegaly […] splenomegaly. […] Genetics […] inheritance pattern […] somatic mutation. […] Mutations […] MDY88 gene. […] Associated conditions […] anemia. […] Epidemiology […] elderly patients […] Caucasian males.

• #57 What Causes Waldenström Macroglobulinemia and How Will It Affect Me? – The Waiting Room

  https://thewaitingroom.karger.com/tell-me-about/what-causes-waldenstrom-macroglobulinemia-and-how-will-it-affect-me/

  Most people develop a condition called IgM monoclonal gammopathy of uncertain significance (IgM MGUS) before WM. […] IgM MGUS becomes more common as people get older, but its cause is unknown. […] Over time (usually years), the monoclonal LPL cells may build up to result in WM, which is eventually diagnosed once symptoms develop, such as fatigue, weight loss, sweats, fevers, nerve damage (peripheral neuropathy) or infections (due to an under-functioning immune system). […] WM is not infectious and cannot be passed on to other people. But blood relatives in the persons immediate family are slightly more likely to develop WM or another kind of B-cell lymphoma. […] Most people with WM (about 90%) have a mutation in the MYD88 gene in the DNA of the LPL cells. […] About 40% of patients with WM have a mutation in the CXCR4 gene, which affects production of a different protein. […] These gene mutations result in abnormal proteins that do not work properly in the bodys cells. […] Everyone who is suspected of having WM ideally should be tested for these gene mutations, as they may affect treatment choices.

• #58 Waldenstrom Macroglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207097-overview

  No definite etiology exists for Waldenstrm macroglobulinemia. Environmental, familial, genetic, and viral factors have been reported. IgM monoclonal gammopathies of undetermined significance (MGUS) are considered a precursor of Waldenstrm macroglobulinemia. […] A possible role for genetic factors has been suggested by reports of familial clustering of Waldenstrm macroglobulinemia. In one study, approximately 20% of 181 serial Waldenstrm macroglobulinemia patients presenting to a tertiary referral had a first-degree relative with either Waldenstrm macroglobulinemia or another B-cell lymphoproliferative disease. Reports of familial cases suggest a genetic predisposition. […] The MYD88 L265P somatic mutation, in which leucine is replaced by proline at position 265, is found in white blood cells in approximately 90% of Waldenstrm macroglobulinemia cases. The mutation results in overactivity of the altered MyD88 protein, stimulating the signaling molecules that activate nuclear factor-kappa-B; this may protect lymphoplasmacytic cells against apoptosis.

• #59 What Causes Waldenström Macroglobulinemia and How Will It Affect Me? – The Waiting Room

  https://thewaitingroom.karger.com/tell-me-about/what-causes-waldenstrom-macroglobulinemia-and-how-will-it-affect-me/

  Most people develop a condition called IgM monoclonal gammopathy of uncertain significance (IgM MGUS) before WM. […] IgM MGUS becomes more common as people get older, but its cause is unknown. […] Over time (usually years), the monoclonal LPL cells may build up to result in WM, which is eventually diagnosed once symptoms develop, such as fatigue, weight loss, sweats, fevers, nerve damage (peripheral neuropathy) or infections (due to an under-functioning immune system). […] WM is not infectious and cannot be passed on to other people. But blood relatives in the persons immediate family are slightly more likely to develop WM or another kind of B-cell lymphoma. […] Most people with WM (about 90%) have a mutation in the MYD88 gene in the DNA of the LPL cells. […] About 40% of patients with WM have a mutation in the CXCR4 gene, which affects production of a different protein. […] These gene mutations result in abnormal proteins that do not work properly in the bodys cells. […] Everyone who is suspected of having WM ideally should be tested for these gene mutations, as they may affect treatment choices.

• #60 What Causes Waldenström Macroglobulinemia and How Will It Affect Me? – The Waiting Room

  https://thewaitingroom.karger.com/tell-me-about/what-causes-waldenstrom-macroglobulinemia-and-how-will-it-affect-me/

  Most people develop a condition called IgM monoclonal gammopathy of uncertain significance (IgM MGUS) before WM. […] IgM MGUS becomes more common as people get older, but its cause is unknown. […] Over time (usually years), the monoclonal LPL cells may build up to result in WM, which is eventually diagnosed once symptoms develop, such as fatigue, weight loss, sweats, fevers, nerve damage (peripheral neuropathy) or infections (due to an under-functioning immune system). […] WM is not infectious and cannot be passed on to other people. But blood relatives in the persons immediate family are slightly more likely to develop WM or another kind of B-cell lymphoma. […] Most people with WM (about 90%) have a mutation in the MYD88 gene in the DNA of the LPL cells. […] About 40% of patients with WM have a mutation in the CXCR4 gene, which affects production of a different protein. […] These gene mutations result in abnormal proteins that do not work properly in the bodys cells. […] Everyone who is suspected of having WM ideally should be tested for these gene mutations, as they may affect treatment choices.

• #61 Facts About Waldenström Macroglobulinemia | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/diseases/waldenstrom-macroglobulinemia/facts-resources.html

  Waldenstrm macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is one type of cancer of the lymph system. […] The exact cause of WM is unknown. You may be at higher risk if any of these is true: […] You have a blood disorder called monoclonal gammopathy of undetermined significance (MGUS). About 1 to 2 percent of people with MGUS will develop a related cancer, like WM, lymphoma or multiple myeloma or another serious condition, like amyloidosis. […] You have a family history of the condition. About 1 in 5 people with WM has a close relative with WM or a related B-cell disease. […] You have hepatitis C. Some, but not all, studies show infection with the hepatitis C virus raises WM risk. […] You have certain autoimmune diseases, such as Sjgren syndrome, which might increase risk. […] Keep in mind that many people who get the disease have none of these risk factors, and most people with these risk factors do not develop the disease.

• #62 Etiology of Waldenström Macroglobulinemia: Genetic Factors and Immune-related Conditions

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7243894/

  Epidemiologic studies provide an insight into the etiology of lymphoplasmacytic lymphoma/Waldenstrm macroglobulinemia, which indicates that repetitive immune stimulation and genetic factors play an important role. […] Although the etiology of WM remains to be better clarified, analysis of emerging data suggests that there may be a link between the immune system and genetic factors that are involved in the development of WM. […] Taken as a whole, our outcomes provide further evidence that supported the hypothesis that chronic stimulation of the immune system is linked to the etiology of WM. […] Familial clustering of LPL/WM is well documented and has been published in case-control cohort studies and multiply affected families. […] Our results expand on previous studies that suggest that there is a role for shared common susceptibility genes that predispose to LPL/WM and certain lymphoproliferative disorders.

• #63 What Causes Waldenström’s Macroglobulinemia: Genetic or Immune-Related Factors, or a Combination?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7020666/

  Population-based studies suggest a role for chronic immune stimulation and genetic factors in the causation of lymphoplasmacytic lymphoma (LPL)/Waldenstrms macroglobulinemia (WM). […] Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors and genetic in the etiology of LPL/WM, which will be reviewed in this paper. […] Taken together, our results support that chronic immune stimulation plays a role in the pathogenesis of LPL/WM. […] Our findings that both personal and family history of Sjgrens syndrome or autoimmune hemolytic anemia were associated with increased risk of LPL/WM indicate that there might be some shared (genetic, environmental, or both) susceptibility for these conditions. […] Together with previous studies, our findings support a role for shared common susceptibility genes that predispose to LPL/WM and certain lymphoproliferative disorders. […] There are a number of gene candidates that could be causing susceptibility to LPL/WM and related conditions. […] Emerging data support a role for germline susceptibility genes in the causation of LPL/WM and other lymphoproliferative disorders.

• #64 Incidence, prevalence, mortality, and causes of death in Waldenström macroglobulinemia: a nationwide, population-based cohort study | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07120-9

  The epidemiological features of Waldenstrm macroglobulinemia (WM) have seldom been investigated at a national level, particularly in East Asia. […] The main cause of death was WM in itself. […] Differences in ethnicity, and geographic variations, exert a considerable influence on the lower incidence of WM in Korea. […] These reports provide evidence that racial differences exist in the incidence of WM, and that environmental and/or genetic factors may have an influence on the development of WM. […] The main cause of death in our cohort was directly attributable to WM, and the magnitude (48.57%) was almost two times higher than that of a previous report from the SEER database (25%). […] The causes of deaths of WM patients are summarized in Table 4. WM-related deaths were recorded as the most common cause, accounting for 102 cases (48.57%). Malignant neoplasms constituted the second most common cause of death, being responsible for 82 deaths (39.05%). Among the 82 deaths due to malignant neoplasms, 23 were due to non-follicular lymphoma, and 22 were due to malignant plasma cell neoplasms.

• #65 Waldenstrom’s macroglobulinemia: An overview

  https://lymphomahub.com/medical-information/waldenstrom-s-macroglobulinemia-an-overview

  To date, the cause of WM is unknown. Research is ongoing to investigate mutations potentially causing B-lymphocyte cells to divide and multiply uncontrollably and overwhelm the production of healthy blood cells. The two mutations are: […] Although the cause remains unknown, several risk factors have been linked to the development of WM, including: previously diagnosed with IgM monoclonal gammopathy of undetermined significance or an autoimmune disease, such as Sjogrens syndrome; or a viral illness, such as hepatitis C; and closely related family members with WM or lymphoma are at higher risk than patients with no genetic relation.

• #66 Waldenstrom macroglobulinemia: prognosis and management | Blood Cancer Journal

  https://www.nature.com/articles/bcj201528

  The addition of elevated 2-microglobulin 4mg/l was associated with a threefold increased risk of death. Of note, the prognostic significance of serum IgM levels and organomegaly has varied in different studies, whereas age is consistently a poor prognostic indicator. […] The combination of purine nucleoside analogs with rituximab improves response rates with little added toxicity, and may be ideal especially when rapid disease control is needed. […] The approval of ibrutinib for WM is exciting, but we need studies in the front-line setting to determine the role of this agent relative to other commonly used regimens in WM. As WM generally has a chronic indolent course, care should be exercised in picking treatments that do not disrupt quality of life. It is therefore important that future studies compare treatment options using patient-reported quality of life outcome measures in addition to standard metrics of depth and duration of response. Finally, we need additional studies to determine the role of the MYD88 L265P mutation in pathogenesis, especially with regard to the role in transformation of IgM MGUS to WM.

• #67 Waldenström’s Macroglobulinemia | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/waldenstroms-macroglobulinemia

  Waldenstrm’s macroglobulinemia (WM) is an uncommon blood cell cancer that originates from malignant B-cells. It is a slow-growing type of non-Hodgkin lymphoma. […] The disease occurs because of an abnormality in B lymphocytes in the bone marrow, causing them to produce too much immunoglobulin protein (IgM) that thickens the blood. […] Up to 20% of WM patients have a first- or second-degree relative with WM or another lymphoma, multiple myeloma, or chronic lymphocytic leukemia. This suggests there may be a genetic risk factor. […] Our colleagues in the Center for Early Detection and Interception of Blood Cancers are studying the genetic and epigenetic factors that characterize conditions that are often precancerous to WM, such as smoldering Waldenstrm’s macroglobulinemia and Monoclonal Gammopathy of Undetermined Significance (MGUS). […] We are credited with discovering the MYD88 and CXCR4 mutations in WM, the approval of the first-ever drug for WM (ibrutinib), and advancing many new drugs through clinical trials.

• #68 Etiology of Waldenström macroglobulinemia: genetic factors and immune-related conditions – University of Miami

  https://scholarship.miami.edu/esploro/outputs/journalArticle/Etiology-of-Waldenstr%C3%B6m-macroglobulinemia-genetic-factors/991031714217302976

  Epidemiologic studies provide an insight into the etiology of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, which indicates that repetitive immune stimulation and genetic factors play an important role. […] Here, the current understanding on the causes of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia are reviewed. […] Recent studies of the literature are discussed, and future population-based studies are proposed to further elucidate the molecular mechanisms that underlie these associations.

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