Materiały źródłowe

• #1 Etiology of Acute Leukemia: A Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8125807/

  Acute leukemias are some of the most common cancers affecting all age groups. Despite a significant improvement made in the treatment of acute leukemias, their cause remains unknown. A number of genetic and environmental factors for the development of acute leukemias have been proposed, but none have been proven. Undoubtedly, genetics have a major role in the development of these diseases. […] A recent two-hit theory for the development of acute lymphoblastic leukemia has been proposed. This combines genetic factors and exposure to infections for the development of this disease. Several genetic factors are suggested. Most recently, for the infection portion, exposure to a virus containing Aspergillus Flavus has been proposed. […] Despite reported differences in race and ethnicity in the incidence and outcome, the underlying causes for this disparities remain poorly understood.

• #2 Etiology of Acute Leukemia: A Review

  https://www.mdpi.com/2072-6694/13/9/2256

  Acute leukemias are some of the most common cancers affecting all age groups. Despite a significant improvement made in the treatment of acute leukemias, their cause remains unknown. A number of genetic and environmental factors for the development of acute leukemias have been proposed, but none have been proven. […] A recent “two-hit” theory for the development of acute lymphoblastic leukemia has been proposed. This combines genetic factors and exposure to infections for the development of this disease. […] The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during preconception, pregnancy and throughout life, have been explored. […] Separate two-hit hypotheses for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis.

• #3 Acute lymphocytic leukemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/symptoms-causes/syc-20369077

  Acute lymphocytic leukemia occurs when a bone marrow cell develops changes (mutations) in its genetic material or DNA. A cell’s DNA contains the instructions that tell a cell what to do. Normally, the DNA tells the cell to grow at a set rate and to die at a set time. In acute lymphocytic leukemia, the mutations tell the bone marrow cell to continue growing and dividing. […] It’s not clear what causes the DNA mutations that can lead to acute lymphocytic leukemia. […] Factors that may increase the risk of acute lymphocytic leukemia include: Previous cancer treatment. Children and adults who’ve had certain types of chemotherapy and radiation therapy for other kinds of cancer may have an increased risk of developing acute lymphocytic leukemia. Exposure to radiation. People exposed to very high levels of radiation, such as survivors of a nuclear reactor accident, have an increased risk of developing acute lymphocytic leukemia. Genetic disorders. Certain genetic disorders, such as Down syndrome, are associated with an increased risk of acute lymphocytic leukemia.

• #4 Acute lymphoblastic leukaemia | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-adults/acute-lymphoblastic-leukaemia/

  Acute lymphoblastic leukaemia is caused by a DNA mutation in the stem cells causing too many white blood cells to be produced. […] The cause or causes of acute leukaemia are uncertain, but known risk factors include: exposure to high levels of radiation, exposure to benzene, a chemical used in manufacturing that is also found in cigarettes. […] It is not known exactly what causes this DNA mutation to occur, but there are a few factors which may increase the risk of developing acute lymphoblastic leukaemia. […] A small number of childhood acute lymphoblastic leukaemia cases are thought to be caused by related genetic disorders. […] Exposure to very high levels of radiation, either before birth or afterwards, is a known risk factor. […] Experts have also carried out extensive research to determine whether the following environmental factors could be a trigger for leukaemia: living near a nuclear power station, living near a power line, living near a building or facility that releases electromagnetic radiation, such as a mobile phone mast.

• #5 Acute Lymphocytic Leukemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459149/

  The etiology of acute lymphocytic leukemia is unknown. However, certain environmental factors have been implicated in the etiology of Acute Lymphocytic Leukemia, such as exposure to benzene, ionizing radiation, or previous exposure to chemotherapy or radiotherapy. […] Genomic studies have noted that somatic, polymorphic variants of ARD5B, IKZF1 (the gene encoding Ikaros), and CDKN2A are associated with an increased risk of ALL (odds ratio 1.3 to 1.9). Other rare germline mutations in PAX5, ETV6, and particularly p53 can also strongly predispose to the development of leukemia. […] Acute lymphoblastic leukemia is not considered a familial disease, and no screening programs have been developed to test for it in childhood.

• #6 Acute Lymphoblastic Leukemia (ALL): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207631-overview

  In a study of the California Cancer Registry it was noted that 3% of patients had a prior known malignancy and that any prior malignancy predisposed to the development of ALL. The prognosis for these patients with secondary ALL was unfavorable compared with that of patients with de novo ALL. […] Cases of ALL with abnormalities of chromosome band 11q23 following treatment with topoisomerase II inhibitors for another malignancy have been described. However, most patients who develop secondary acute leukemia after chemotherapy for another cancer develop AML rather than ALL. […] A genome-wide association study of susceptibility to ALL in adolescents and young adults identified a significant susceptibility locus in GATA3: rs3824662 (odds ratio 1.77) and rs3781093 (OR 1.73). Other studies have shown increased risk of ALL in association with polymorphisms of the following: Arylamine N-acetyltransferases 1 and 2, MMP-8 promoter genotypes, HLA alleles, ARID5B, IKZF1, CEBPE, CDKN2A, PIP4K2A, LHPP, ELK3.

• #7 What Causes Acute Lymphocytic Leukemia (ALL)? | American Cancer Society

  https://www.cancer.org/cancer/types/acute-lymphocytic-leukemia/causes-risks-prevention/what-causes.html

  Some people with acute lymphocytic leukemia (ALL) have one or more of the known risk factors, but many do not. Even when a person has one or more risk factors, it can be very hard to know if it actually caused the leukemia. […] Great progress has been made in understanding how certain changes in the DNA in normal bone marrow cells can cause them to become leukemia cells. […] Cancers (including ALL) can be caused by mutations (changes) that turn on oncogenes or turn off tumor suppressor genes. […] Several types of chromosome changes may be found in ALL cells: […] Translocations are the most common type of chromosome change that can lead to leukemia. […] The most common translocation in ALL in adults is known as the Philadelphia chromosome, which is a swap of DNA between chromosomes 9 and 22, abbreviated as t(9;22).

• #8 Acute Lymphoblastic Leukemia – Causes/Risk Factors

  https://www.medindia.net/health/conditions/acute-lymphoblastic-leukemia-causes.htm

  The causes of Acute Lymphoblastic Leukemia are not very clear. Researchers have indicated that ALL is caused by a combination of genetic, biologic, and environmental factors. […] Few of the risk factors / causes indicated for ALL are- […] Children with Down syndrome harbor a several-fold increased risk for developing acute leukemia (both ALL and AML). ALL is more common among the Down Syndrome patients. Outcome for Down syndrome children affected by ALL has generally been reported as poorer than that of nonDown syndrome children. […] Certain other genetic conditions that have been implicated are: Neurofibromatosis, Shwachman syndrome, Bloom’s syndrome, Ataxia telangiectasia, Myelodysplastic syndrome, Myeloproliferative disorders. A number of mutations have been associated with ALL. Translocations, or the rearrangement of genes between two chromosomes, have been associated with upto 65% of all leukemias. The most common mutation in ALL is t (12:21). Occurs in 20% of ALL patients. Philadelphia (Ph) chromosome [t(9;22)] is observed in 5% children and in 20% adults with ALL.

• #9 A causal mechanism for childhood acute lymphoblastic leukaemia | Nature Reviews Cancer

  https://www.nature.com/articles/s41568-018-0015-6

  In this Review, I present evidence supporting a multifactorial causation of childhood acute lymphoblastic leukaemia (ALL), a major subtype of paediatric cancer. […] ALL evolves in two discrete steps. First, in utero initiation by fusion gene formation or hyperdiploidy generates a covert, pre-leukaemic clone. Second, in a small fraction of these cases, the postnatal acquisition of secondary genetic changes (primarily V(D)J recombination-activating protein (RAG) and activation-induced cytidine deaminase (AID)-driven copy number alterations in the case of ETS translocation variant 6 (ETV6) runt-related transcription factor 1 (RUNX1)+ ALL) drives conversion to overt leukaemia. […] Epidemiological and modelling studies endorse a dual role for common infections. Microbial exposures earlier in life are protective but, in their absence, later infections trigger the critical secondary mutations.

• #10 Acute Lymphoblastic Leukemia (ALL): Symptoms, Treatment & Prognosis

  https://my.clevelandclinic.org/health/diseases/21564-acute-lymphocytic-leukemia

  People with the following inherited conditions have a higher risk of ALL than people who dont have the conditions: Ataxia telangiectasia, Bloom syndrome, Down syndrome, Fanconi anemia, Klinefelter syndrome, Li-Fraumeni syndrome, Neurofibromatosis type-1 (NF1), Wiskott-Aldrich syndrome. […] No, it cant. Children with ALL develop the condition because of genetic changes that happened before they were born. But adults with ALL may be able to lower their risk by avoiding carcinogens, including tobacco and toxic chemicals.

• #11 Childhood Acute Lymphoblastic Leukemia – NCI

  https://www.cancer.gov/types/leukemia/patient/child-all-treatment-pdq

  Childhood ALL is caused by changes to how the blood stem cells function, especially how they grow and divide into new cells. The exact cause of these cell changes is often unknown. […] A risk factor is anything that increases the chance of getting a disease. Not every child with one or more of these risk factors will develop ALL. And it will develop in some children who don’t have a known risk factor. Risk factors may be genetic or due to other causes. […] Possible genetic risk factors for ALL include: Down syndrome, neurofibromatosis type 1, Bloom syndrome, Fanconi anemia, ataxia-telangiectasia, Li-Fraumeni syndrome (TP53 gene), constitutional mismatch repair deficiency (mutations in certain genes that stop DNA from repairing itself, which leads to the growth of cancers at an early age), having certain changes in chromosomes or genes. […] Other possible risk factors for ALL include: being exposed to x-rays before birth, being exposed to radiation, past treatment with chemotherapy.

• #12 Risks and causes for acute lymphoblastic leukaemia (ALL)

  https://www.cancerresearchuk.org/about-cancer/acute-lymphoblastic-leukaemia-all/risks-causes

  Your risk of developing cancer depends on many things. These can include environmental, lifestyle and genetic factors. […] We dont know what causes most cases of acute lymphoblastic leukaemia (ALL). But there are some factors that may increase your risk of developing it. These include certain genetic conditions, previous chemotherapy treatment and ionising radiation. […] Some rare, inherited conditions can increase the risk of acute leukaemia, including: Downs syndrome, Fanconi anaemia, ataxia telangiectasia, Bloom syndrome. […] People who have had certain chemotherapy in the past have a slightly increased risk of developing leukaemia some years later. […] High energy (ionising) radiation can cause cancer because it can affect your cells and damage the DNA. Research suggests that children who have had radiotherapy have a slightly increased risk of developing leukaemia later in life.

• #13 Acute Lymphoblastic Leukemia | Info About This Cancer | LLS

  https://www.lls.org/leukemia/acute-lymphoblastic-leukemia

  Is a cancer of the bone marrow and blood. […] Does not have a clear cause. […] Doctors don’t know why some cells become leukemic cells and others don’t. Usually DNA mutations associated with ALL occur during a person’s lifetime rather than being inherited from a parent. For most people who have acute lymphoblastic leukemia (ALL), there are no obvious reasons why they developed the disease. […] Risk factors associated with the disease include: Previous exposure to chemotherapy and radiation therapy. […] Genetic disorders including: Down syndrome, neurofibromatosis, Klinefelter syndrome, Fanconi anemia, Schwachman-Diamond syndrome, Bloom syndrome, Li-Fraumeni syndrome, and ataxia telangiectasia have been associated with an increased risk of developing ALL. […] Age. The highest incidence rates for ALL are seen in children and adolescents younger than 15 years. […] Sex. Males are more likely to develop ALL than females. […] Race/ethnicity. In the United States, ALL is more common in Hispanics and whites. […] Currently, there’s no way to prevent the disease. You can’t catch ALL from someone else.

• #14

  https://continentalhospitals.com/diseases/acute-lymphoblastic-leukemia/

  Acute Lymphoblastic Leukemia (ALL) is a type of cancer that affects the blood and bone marrow. […] Genetic Mutations: Changes in DNA within bone marrow cells can lead to uncontrolled cell growth, increasing the risk of ALL. […] Inherited Genetic Syndromes: Conditions like Down syndrome, Li-Fraumeni syndrome, and neurofibromatosis increase the likelihood of ALL. […] Radiation Exposure: High levels of radiation exposure, such as from previous cancer treatments or nuclear accidents, may increase risk. […] Chemotherapy for Other Cancers: Certain chemotherapy drugs can raise the risk of developing secondary leukemia, including ALL. […] Viral Infections: Some studies suggest a link between viral infections, such as the Epstein-Barr virus, and an increased risk of leukemia. […] Weakened Immune System: People with compromised immune systems (e.g., from immunosuppressive medications) may have a higher risk.

• #15 Acute Lymphocytic Leukemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459149/

  The etiology of acute lymphocytic leukemia is unknown. However, certain environmental factors have been implicated in the etiology of Acute Lymphocytic Leukemia, such as exposure to benzene, ionizing radiation, or previous exposure to chemotherapy or radiotherapy. […] Genomic studies have noted that somatic, polymorphic variants of ARD5B, IKZF1 (the gene encoding Ikaros), and CDKN2A are associated with an increased risk of ALL (odds ratio 1.3 to 1.9). Other rare germline mutations in PAX5, ETV6, and particularly p53 can also strongly predispose to the development of leukemia. […] Acute lymphoblastic leukemia is not considered a familial disease, and no screening programs have been developed to test for it in childhood.

• #16 Risk Factors for Acute Lymphocytic Leukemia (ALL) | American Cancer Society

  https://www.cancer.org/cancer/types/acute-lymphocytic-leukemia/causes-risks-prevention/risk-factors.html

  In general, leukemia is more common in men than women. This includes ALL that is more common in males than in females. […] Someone who has an identical twin who develops ALL in the first year of life has an increased risk of getting ALL. […] Other factors that have been studied for a possible link to ALL include exposure to electromagnetic fields, workplace exposure to diesel, gasoline, pesticides, and certain other chemicals, smoking, and exposure to hair dyes.

• #17 Etiology of Acute Leukemia: A Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8125807/

  Undoubtedly, genetics plays a major role in the etiology of leukemia. […] While for the majority of leukemia cases there are no obvious known predisposing factors, some genetic and acquired germline mutations and clonal chromosomal abnormalities are associated with increased incidence of leukemia. […] The major inherited and genetic disorders resulting in a predisposition to acute leukemia are summarized in Table 1. […] DNA damage and impaired DNA damage repair capacity during proliferative DNA replication can result in mutations leading to the initiation of malignant transformation. […] A large number of environmental causes for the development of leukemia have been suggested. These mostly involve exposure to cancer-causing agents, including chemicals, infections and radiation during various stages of life.

• #18 Risk Factors for Acute Lymphocytic Leukemia (ALL) | American Cancer Society

  https://www.cancer.org/cancer/types/acute-lymphocytic-leukemia/causes-risks-prevention/risk-factors.html

  Radiation exposure is a risk factor for both ALL and acute myeloid leukemia (AML). For example, Japanese atomic bomb survivors had a greatly increased risk of developing acute leukemia. […] The risk of ALL may be increased by exposure to certain chemotherapy drugs and certain other chemicals, including benzene. […] Infection with the human T-cell lymphoma/leukemia virus-1 (HTLV-1) can cause a rare type of T-cell ALL. […] In Africa, the Epstein-Barr virus (EBV) has been linked to Burkitt lymphoma, as well as to a form of ALL. […] There are some genetic syndromes (some of which can be inherited from a parent) that seem to raise the risk of ALL. […] ALL is more likely to occur in children and in adults over the age of 50. […] ALL is more common in White individuals than in African Americans, but the reasons for this are not clear.

• #19 Acute Lymphocytic Leukemia (ALL): Symptoms, Risks, and Survival Rates

  https://www.healthline.com/health/acute-lymphocytic-leukemia-all

  The causes of ALL arent yet known. […] Although doctors dont yet know the specific causes of ALL, they have identified a few risk factors of the condition. […] People whove been exposed to high levels of radiation, such as those whove survived a nuclear reactor accident, have shown an increased risk for ALL. […] According to a study from 1994, Japanese survivors of the atomic bomb in World War II had an increased risk of acute leukemia six to eight years after exposure. A 2013 follow-up study reinforced the connection between atomic bomb exposure and the risk of developing leukemia. […] Prolonged exposure to certain chemicals, such as benzene or chemotherapy drugs, is strongly correlated to the development of ALL. […] A 2010 study reports that various viral infections have been linked to an increased risk for ALL.

• #20 Acute lymphoblastic leukaemia | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-adults/acute-lymphoblastic-leukaemia/

  Acute lymphoblastic leukaemia is caused by a DNA mutation in the stem cells causing too many white blood cells to be produced. […] The cause or causes of acute leukaemia are uncertain, but known risk factors include: exposure to high levels of radiation, exposure to benzene, a chemical used in manufacturing that is also found in cigarettes. […] It is not known exactly what causes this DNA mutation to occur, but there are a few factors which may increase the risk of developing acute lymphoblastic leukaemia. […] A small number of childhood acute lymphoblastic leukaemia cases are thought to be caused by related genetic disorders. […] Exposure to very high levels of radiation, either before birth or afterwards, is a known risk factor. […] Experts have also carried out extensive research to determine whether the following environmental factors could be a trigger for leukaemia: living near a nuclear power station, living near a power line, living near a building or facility that releases electromagnetic radiation, such as a mobile phone mast.

• #21 Acute lymphoblastic leukaemia | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-adults/acute-lymphoblastic-leukaemia/

  Exposure to the chemical benzene is a known risk factor for adult acute leukaemia. […] There is some evidence to show an increased risk of acute lymphoblastic leukaemia in people who are obese or have a weakened immune system due to HIV or AIDS or taking immunosuppressants after an organ transplant.

• #22 Acute Lymphoblastic Leukemia (ALL): Symptoms, Diagnosis, Treatment, Prognosis, and Survival Rate

  https://www.webmd.com/cancer/lymphoma/acute-lymphoblastic-leukemia

  Acute lymphoblastic leukemia (ALL) is a type of blood cancer that starts in white blood cells in your bone marrow, the soft inner part of your bones. […] Doctors dont know what causes most cases of ALL. But research has found that certain things might raise your risk, including: […] Contact with high levels of radiation to treat other types of cancer […] Contact with chemicals such as benzene, a solvent used in oil refineries and other industries and found in cigarette smoke; and some cleaning products, detergents, and paint strippers […] Infection with the human T-cell lymphoma/leukemia virus-1 (HTLV-1) or the Epstein-Barr virus (EBV), mostly outside the U.S. […] Having a medical condition thats tied to your genes, such as Down syndrome […] Being white […] Being male.

• #23 Leukemia: Symptoms, Signs, Causes, Types & Treatment

  https://my.clevelandclinic.org/health/diseases/4365-leukemia

  Leukemia starts when the DNA of a single cell in your bone marrow changes (mutates) and cant develop and function normally. […] Leukemia starts when the DNA of a single cell in your bone marrow changes (mutates). DNA is the instruction code that tells a cell when to grow, how to develop and when to die. Because of the mutation, or coding error, leukemia cells keep multiplying. All cells arising from the original mutated cell also have the mutated DNA. […] Scientists dont know what causes these developing cells to mutate. Theyve been able to identify some common mutations that people diagnosed with different types of leukemia share. […] Studies have shown that certain factors may increase your risk, including: Previous cancer treatment. Past cancer treatments involving radiation or chemotherapy may increase the likelihood youll develop some types of leukemia.

• #24 Acute Lymphoblastic Leukemia (ALL): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207631-overview

  Less is known about the etiology of ALL in adults, compared with acute myeloid leukemia (AML). Most adults with ALL have no identifiable risk factors. […] Although most leukemias occurring after exposure to radiation are AML rather than ALL, an increased prevalence of ALL was noted in survivors of the Hiroshima atomic bomb but not in those who survived the Nagasaki atomic bomb. […] Analysis of the Surveillance, Epidemiology and End Results (SEER) database showed that the incidence of ALL was higher than expected in patients with a prior history of Hodgkin lymphoma, small cell lung cancer, and ovarian cancer. […] Rare patients have an antecedent hematologic disorder (AHD) such as myelodysplastic syndrome (MDS) that evolves to ALL. However, most patients with MDS that evolves to acute leukemia develop AML rather than ALL. Some patients receiving lenalidomide as maintenance therapy for multiple myeloma have developed secondary ALL.

• #25 Acute Lymphoblastic Leukemia (ALL): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207631-overview

  In a study of the California Cancer Registry it was noted that 3% of patients had a prior known malignancy and that any prior malignancy predisposed to the development of ALL. The prognosis for these patients with secondary ALL was unfavorable compared with that of patients with de novo ALL. […] Cases of ALL with abnormalities of chromosome band 11q23 following treatment with topoisomerase II inhibitors for another malignancy have been described. However, most patients who develop secondary acute leukemia after chemotherapy for another cancer develop AML rather than ALL. […] A genome-wide association study of susceptibility to ALL in adolescents and young adults identified a significant susceptibility locus in GATA3: rs3824662 (odds ratio 1.77) and rs3781093 (OR 1.73). Other studies have shown increased risk of ALL in association with polymorphisms of the following: Arylamine N-acetyltransferases 1 and 2, MMP-8 promoter genotypes, HLA alleles, ARID5B, IKZF1, CEBPE, CDKN2A, PIP4K2A, LHPP, ELK3.

• #26 Risk Factors for Acute Lymphocytic Leukemia (ALL) | American Cancer Society

  https://www.cancer.org/cancer/types/acute-lymphocytic-leukemia/causes-risks-prevention/risk-factors.html

  Radiation exposure is a risk factor for both ALL and acute myeloid leukemia (AML). For example, Japanese atomic bomb survivors had a greatly increased risk of developing acute leukemia. […] The risk of ALL may be increased by exposure to certain chemotherapy drugs and certain other chemicals, including benzene. […] Infection with the human T-cell lymphoma/leukemia virus-1 (HTLV-1) can cause a rare type of T-cell ALL. […] In Africa, the Epstein-Barr virus (EBV) has been linked to Burkitt lymphoma, as well as to a form of ALL. […] There are some genetic syndromes (some of which can be inherited from a parent) that seem to raise the risk of ALL. […] ALL is more likely to occur in children and in adults over the age of 50. […] ALL is more common in White individuals than in African Americans, but the reasons for this are not clear.

• #27 Acute Lymphoblastic Leukemia (ALL): Symptoms, Treatment & Prognosis

  https://my.clevelandclinic.org/health/diseases/21564-acute-lymphocytic-leukemia

  Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow. […] Researchers continue to find genetic mutations (changes) that cause ALL. Young children with ALL may have had genetic changes that happened before they were born. Some people have ALL because they inherited conditions that increase their chance of developing the disease. ALL in adults is linked to some carcinogens, including tobacco. […] Risk factors include: Girls age 1 and younger have a higher risk than boys of the same age. After age 1, the risk is higher for males. People who are white are somewhat more likely to develop ALL than people who are Black. Children exposed to radiation in utero have an increased risk of ALL. Likewise, children and adults who had radiation therapy for other cancers have increased ALL risk. Some viral infections, including Epstein-Barr virus or human T-cell leukemia virus, increase your risk of developing ALL.

• #28 Acute lymphoblastic leukemia: an overview of etiology, epidemiology, pathophysiology, diagnosis, and treatment

  https://lymphoblastic-hub.com/medical-information/acute-lymphoblastic-leukemia-an-overview-of-etiology-epidemiology-pathophysiology-diagnosis-and-treatment

  The etiology of ALL is currently unknown; however, there are various environmental risk factors and several genetic syndromes that predispose some individuals to ALL: […] Congenital syndromes include Downs syndrome, Fanconi anaemia, ataxia telangiectasia, Bloom syndrome, Nijmegen breakage syndrome; […] Environmental risk factors include exposure to benzene, ionising radiation, or previous exposure to chemotherapy or radiotherapy. […] Pesticide exposure and certain solvents or infections, such as Epstein-Barr virus and human immunodeficiencies.

• #29 A causal mechanism for childhood acute lymphoblastic leukaemia | Nature Reviews Cancer

  https://www.nature.com/articles/s41568-018-0015-6

  In this Review, I present evidence supporting a multifactorial causation of childhood acute lymphoblastic leukaemia (ALL), a major subtype of paediatric cancer. […] ALL evolves in two discrete steps. First, in utero initiation by fusion gene formation or hyperdiploidy generates a covert, pre-leukaemic clone. Second, in a small fraction of these cases, the postnatal acquisition of secondary genetic changes (primarily V(D)J recombination-activating protein (RAG) and activation-induced cytidine deaminase (AID)-driven copy number alterations in the case of ETS translocation variant 6 (ETV6) runt-related transcription factor 1 (RUNX1)+ ALL) drives conversion to overt leukaemia. […] Epidemiological and modelling studies endorse a dual role for common infections. Microbial exposures earlier in life are protective but, in their absence, later infections trigger the critical secondary mutations.

• #30 Etiology of Acute Leukemia: A Review

  https://www.mdpi.com/2072-6694/13/9/2256

  A recent two-hit theory combines genetic mutation and exposure to one or more infections for the genesis of ALL. The revised two-hit hypothesis for the development of precursor B-cell ALL hypothesizes that this disease arises through a two-step process. The first step is a predisposing genetic mutation. The second step suggests exposure to one or more infections. […] This study may indicate that mycovirus containing Aspergillus Flavus can directly affect cells of ALL patients in remission and alter and transform the genetic and cell surface makers of their presumably genetically susceptible cells, and not controls. The report also indicates that in limited studies, when cultures with and without EBV were irradiated, this had significantly increased the co-expression of CD10/CD19, which is considered as one of the characteristic cell surface phenotypes in the ALL. […] Considering the two-hit theory for the development of acute lymphoblastic leukemia, it is postulated that the mycovirus containing Aspergillus Flavus may provide a consistent organism in the mechanism of leukemogenesis in acute lymphoblastic leukemia.

• #31 Acute Lymphoblastic Leukemia (ALL): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207631-overview

  A proposed mechanism for some cases of childhood ALL is a two-step process of genetic mutation and exposure to infection. In contrast, most adults with ALL have no identifiable risk factors. […] A review of the genetics, cell biology, immunology, and epidemiology of childhood leukemia by Greaves concluded that B-cell precursor ALL has a multifactorial etiology, with a two-step process of genetic mutation and exposure to infection playing a prominent role. The first step occurs in utero, when fusion gene formation or hyperdiploidy generates a covert, pre-leukemic clone. The second step is the postnatal acquisition of secondary genetic changes that drive conversion to overt leukemia. Only 1% of children born with a pre-leukemic clone progress to leukemia. […] The second step is triggered by infection. Triggering is more likely to occur in children whose immune response is abnormally regulated because they were not exposed to infections in the first few weeks and months of life. Lack of exposure to these early infections, which prime the immune system, is more likely to occur in societies that are zealous about hygiene; this would help explain why at present, pediatric ALL is seen primarily in industrialized societies.

• #32 Etiology of Acute Leukemia: A Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8125807/

  The effects of ionizing radiation in the development of leukemia at various phases of life, including preconception, in utero, and post-natal exposures, have been proposed, and various examples have been published. […] Individuals who have received chemotherapy for the treatment of cancer, with or without radiation, have an increased risk of leukemia. […] Infections, including bacterial, viral and fungal agents alone, and in conjunction with genetic mutations, have been implicated in leukemogenesis. […] A recent two-hit theory combines genetic mutation and exposure to one or more infections for the genesis of ALL. […] This proposal, therefore, hypothesizes that the process of developing ALL begins in utero by fusion gene formation or hyperdiploidy and preparation of pre-leukemic clone. […] Recent reports suggest a mycovirus containing Aspergillus flavus as one of the possible candidates for the infection category.

• #33 A causal mechanism for childhood acute lymphoblastic leukaemia | Nature Reviews Cancer

  https://www.nature.com/articles/s41568-018-0015-6

  In this Review, I present evidence supporting a multifactorial causation of childhood acute lymphoblastic leukaemia (ALL), a major subtype of paediatric cancer. […] ALL evolves in two discrete steps. First, in utero initiation by fusion gene formation or hyperdiploidy generates a covert, pre-leukaemic clone. Second, in a small fraction of these cases, the postnatal acquisition of secondary genetic changes (primarily V(D)J recombination-activating protein (RAG) and activation-induced cytidine deaminase (AID)-driven copy number alterations in the case of ETS translocation variant 6 (ETV6) runt-related transcription factor 1 (RUNX1)+ ALL) drives conversion to overt leukaemia. […] Epidemiological and modelling studies endorse a dual role for common infections. Microbial exposures earlier in life are protective but, in their absence, later infections trigger the critical secondary mutations.

• #34 Acute Lymphoblastic Leukemia (ALL): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207631-overview

  A proposed mechanism for some cases of childhood ALL is a two-step process of genetic mutation and exposure to infection. In contrast, most adults with ALL have no identifiable risk factors. […] A review of the genetics, cell biology, immunology, and epidemiology of childhood leukemia by Greaves concluded that B-cell precursor ALL has a multifactorial etiology, with a two-step process of genetic mutation and exposure to infection playing a prominent role. The first step occurs in utero, when fusion gene formation or hyperdiploidy generates a covert, pre-leukemic clone. The second step is the postnatal acquisition of secondary genetic changes that drive conversion to overt leukemia. Only 1% of children born with a pre-leukemic clone progress to leukemia. […] The second step is triggered by infection. Triggering is more likely to occur in children whose immune response is abnormally regulated because they were not exposed to infections in the first few weeks and months of life. Lack of exposure to these early infections, which prime the immune system, is more likely to occur in societies that are zealous about hygiene; this would help explain why at present, pediatric ALL is seen primarily in industrialized societies.

• #35 Etiology of Acute Leukemia: A Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8125807/

  The effects of ionizing radiation in the development of leukemia at various phases of life, including preconception, in utero, and post-natal exposures, have been proposed, and various examples have been published. […] Individuals who have received chemotherapy for the treatment of cancer, with or without radiation, have an increased risk of leukemia. […] Infections, including bacterial, viral and fungal agents alone, and in conjunction with genetic mutations, have been implicated in leukemogenesis. […] A recent two-hit theory combines genetic mutation and exposure to one or more infections for the genesis of ALL. […] This proposal, therefore, hypothesizes that the process of developing ALL begins in utero by fusion gene formation or hyperdiploidy and preparation of pre-leukemic clone. […] Recent reports suggest a mycovirus containing Aspergillus flavus as one of the possible candidates for the infection category.

• #36 Etiology of Acute Leukemia: A Review

  https://www.mdpi.com/2072-6694/13/9/2256

  A recent two-hit theory combines genetic mutation and exposure to one or more infections for the genesis of ALL. The revised two-hit hypothesis for the development of precursor B-cell ALL hypothesizes that this disease arises through a two-step process. The first step is a predisposing genetic mutation. The second step suggests exposure to one or more infections. […] This study may indicate that mycovirus containing Aspergillus Flavus can directly affect cells of ALL patients in remission and alter and transform the genetic and cell surface makers of their presumably genetically susceptible cells, and not controls. The report also indicates that in limited studies, when cultures with and without EBV were irradiated, this had significantly increased the co-expression of CD10/CD19, which is considered as one of the characteristic cell surface phenotypes in the ALL. […] Considering the two-hit theory for the development of acute lymphoblastic leukemia, it is postulated that the mycovirus containing Aspergillus Flavus may provide a consistent organism in the mechanism of leukemogenesis in acute lymphoblastic leukemia.

• #37 Acute Lymphoblastic Leukemia | Acute Lymphocytic Leukemia | MedlinePlus

  https://medlineplus.gov/acutelymphocyticleukemia.html

  Acute lymphocytic leukemia is a type of acute leukemia. It’s also called ALL and acute lymphoblastic leukemia. „Acute” means that it usually gets worse quickly if it’s not treated. ALL is the most common type of cancer in children. It can also affect adults. […] ALL happens when there are changes in the genetic material (DNA) in bone marrow cells. The cause of these genetic changes is unknown. However, there are certain factors that raise your risk of ALL. […] The factors that raise your risk of ALL include: Being male, Being white, Being over age 70, Having had chemotherapy or radiation therapy, Having been exposed to high levels of radiation, Having certain genetic disorders, such as Down syndrome.

• #38 Risk Factors for Acute Lymphocytic Leukemia (ALL) | American Cancer Society

  https://www.cancer.org/cancer/types/acute-lymphocytic-leukemia/causes-risks-prevention/risk-factors.html

  Radiation exposure is a risk factor for both ALL and acute myeloid leukemia (AML). For example, Japanese atomic bomb survivors had a greatly increased risk of developing acute leukemia. […] The risk of ALL may be increased by exposure to certain chemotherapy drugs and certain other chemicals, including benzene. […] Infection with the human T-cell lymphoma/leukemia virus-1 (HTLV-1) can cause a rare type of T-cell ALL. […] In Africa, the Epstein-Barr virus (EBV) has been linked to Burkitt lymphoma, as well as to a form of ALL. […] There are some genetic syndromes (some of which can be inherited from a parent) that seem to raise the risk of ALL. […] ALL is more likely to occur in children and in adults over the age of 50. […] ALL is more common in White individuals than in African Americans, but the reasons for this are not clear.

• #39 Acute Lymphoblastic Leukemia (ALL): Symptoms, Treatment & Prognosis

  https://my.clevelandclinic.org/health/diseases/21564-acute-lymphocytic-leukemia

  Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow. […] Researchers continue to find genetic mutations (changes) that cause ALL. Young children with ALL may have had genetic changes that happened before they were born. Some people have ALL because they inherited conditions that increase their chance of developing the disease. ALL in adults is linked to some carcinogens, including tobacco. […] Risk factors include: Girls age 1 and younger have a higher risk than boys of the same age. After age 1, the risk is higher for males. People who are white are somewhat more likely to develop ALL than people who are Black. Children exposed to radiation in utero have an increased risk of ALL. Likewise, children and adults who had radiation therapy for other cancers have increased ALL risk. Some viral infections, including Epstein-Barr virus or human T-cell leukemia virus, increase your risk of developing ALL.

• #40 Acute Lymphoblastic Leukemia | Info About This Cancer | LLS

  https://www.lls.org/leukemia/acute-lymphoblastic-leukemia

  Is a cancer of the bone marrow and blood. […] Does not have a clear cause. […] Doctors don’t know why some cells become leukemic cells and others don’t. Usually DNA mutations associated with ALL occur during a person’s lifetime rather than being inherited from a parent. For most people who have acute lymphoblastic leukemia (ALL), there are no obvious reasons why they developed the disease. […] Risk factors associated with the disease include: Previous exposure to chemotherapy and radiation therapy. […] Genetic disorders including: Down syndrome, neurofibromatosis, Klinefelter syndrome, Fanconi anemia, Schwachman-Diamond syndrome, Bloom syndrome, Li-Fraumeni syndrome, and ataxia telangiectasia have been associated with an increased risk of developing ALL. […] Age. The highest incidence rates for ALL are seen in children and adolescents younger than 15 years. […] Sex. Males are more likely to develop ALL than females. […] Race/ethnicity. In the United States, ALL is more common in Hispanics and whites. […] Currently, there’s no way to prevent the disease. You can’t catch ALL from someone else.

• #41 Types of Leukemia: Common, Rare & More

  https://www.cancercenter.com/cancer-types/leukemia/types

  Acute lymphocytic leukemia progresses rapidly, replacing healthy cells that produce functional lymphocytes with leukemia cells that can’t mature properly. […] ALL develops when changes in DNA (mutations) cause the bone marrow to produce too many abnormal lymphocytes (a type of white blood cell). […] Its unknown what exactly causes the mutations that lead to ALL, but certain factors may increase ones risk. Risk factors for ALL include: Being male, white and older than 70 years old; Having a history of chemotherapy or radiation exposure.

• #42 Etiology of Acute Leukemia: A Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8125807/

  Acute leukemias are some of the most common cancers affecting all age groups. Despite a significant improvement made in the treatment of acute leukemias, their cause remains unknown. A number of genetic and environmental factors for the development of acute leukemias have been proposed, but none have been proven. Undoubtedly, genetics have a major role in the development of these diseases. […] A recent two-hit theory for the development of acute lymphoblastic leukemia has been proposed. This combines genetic factors and exposure to infections for the development of this disease. Several genetic factors are suggested. Most recently, for the infection portion, exposure to a virus containing Aspergillus Flavus has been proposed. […] Despite reported differences in race and ethnicity in the incidence and outcome, the underlying causes for this disparities remain poorly understood.

• #43 Risk Factors for Acute Lymphocytic Leukemia (ALL) | American Cancer Society

  https://www.cancer.org/cancer/types/acute-lymphocytic-leukemia/causes-risks-prevention/risk-factors.html

  In general, leukemia is more common in men than women. This includes ALL that is more common in males than in females. […] Someone who has an identical twin who develops ALL in the first year of life has an increased risk of getting ALL. […] Other factors that have been studied for a possible link to ALL include exposure to electromagnetic fields, workplace exposure to diesel, gasoline, pesticides, and certain other chemicals, smoking, and exposure to hair dyes.

• #44 Acute Lymphocytic Leukemia (ALL): Symptoms, Risks, and Survival Rates

  https://www.healthline.com/health/acute-lymphocytic-leukemia-all

  ALL doesnt appear to be an inherited disease. However, some inherited syndromes exist with genetic changes that raise the risk of ALL. […] Some populations have a higher risk for ALL, although these differences in risk arent yet well-understood. […] Experts have also studied the following as possible links to developing ALL: cigarette smoking, long exposure to diesel fuel, gasoline, pesticides, electromagnetic fields.

• #45 Acute lymphoblastic leukaemia | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-adults/acute-lymphoblastic-leukaemia/

  Exposure to the chemical benzene is a known risk factor for adult acute leukaemia. […] There is some evidence to show an increased risk of acute lymphoblastic leukaemia in people who are obese or have a weakened immune system due to HIV or AIDS or taking immunosuppressants after an organ transplant.

• #46 Acute lymphoblastic leukemia – Wikipedia

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

  In most cases, the cause is unknown. […] Genetic risk factors may include Down syndrome, Li-Fraumeni syndrome, or neurofibromatosis type 1. […] Environmental risk factors may include significant radiation exposure or prior chemotherapy. […] Evidence regarding electromagnetic fields or pesticides is unclear. […] Some hypothesize that an abnormal immune response to a common infection may be a trigger. […] The underlying mechanism involves multiple genetic mutations that results in rapid cell division. […] ALL emerges when a single lymphoblast gains many mutations to genes that affect blood cell development and proliferation. […] Environmental risk factors are also needed to help create enough genetic mutations to cause disease. […] High levels of radiation exposure from nuclear fallout is a known risk factor for developing leukemia.

• #47 Acute lymphoblastic leukemia – Wikipedia

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

  Evidence whether lesser radiation, as from x-ray imaging during pregnancy, increases the risk of disease remains inconclusive. […] Exposure to strong electromagnetic radiation from power lines has also been associated with a slightly increased ALL risk. […] High birth weight (greater than 4000 g or 8.8 lbs) is also associated with a small increased risk. […] Evidence suggests that secondary leukemia can develop in individuals treated with certain types of chemotherapy, such as epipodophyllotoxins and cyclophosphamide. […] There is some evidence that a common infection, such as influenza, may indirectly promote the emergence of ALL. […] The delayed-infection hypothesis states that ALL results from an abnormal immune response to infection in a person with genetic risk factors.

• #48

  https://ijpbms.com/index.php/ijpbms/article/view/373

  Acute Lymphoblastic Leukemia (ALL) is a malignancy of the blood and bone marrow affecting both adults and children. Despite significant advancements in the treatment of ALL, its etiology remains multifactorial and complex. […] The etiology of Acute Lymphoblastic Leukemia remains a complex puzzle, tightly intertwined with a combination of genetic, environmental, and lifestyle factors. While significant progress has been made in identifying key genetic alterations and environmental exposures associated with ALL, further research is essential to understand the intricate interplay between genetic predispositions and environmental triggers. Improved understanding of the causes of ALL will aid in developing effective preventive strategies, targeted therapies, and personalized treatment approaches, ultimately reducing the burden of this devastating disease.

• #49 What Causes Acute Lymphocytic Leukemia (ALL)? | American Cancer Society

  https://www.cancer.org/cancer/types/acute-lymphocytic-leukemia/causes-risks-prevention/what-causes.html

  In many cases of ALL, the gene changes that lead to the leukemia are not known. […] Although this can happen sometimes with ALL, such as with some of the genetic syndromes listed in Risk Factors for Acute Lymphocytic Leukemia (ALL), inherited mutations are not a common cause of ALL. […] Usually DNA mutations related to ALL are acquired during the persons lifetime, rather than having been inherited. They may result from outside causes like exposure to radiation or cancer-causing chemicals, but in most cases the reason they occur isn’t clear.

• #50 A causal mechanism for childhood acute lymphoblastic leukaemia | Nature Reviews Cancer

  https://www.nature.com/articles/s41568-018-0015-6

  Risk is further modified by inherited genetics, chance and, probably, diet. […] Childhood ALL can be viewed as a paradoxical consequence of progress in modern societies, where behavioural changes have restrained early microbial exposure. […] This engenders an evolutionary mismatch between historical adaptations of the immune system and contemporary lifestyles. […] Childhood ALL may be a preventable cancer.

• #51

  https://ijpbms.com/index.php/ijpbms/article/view/373

  Acute Lymphoblastic Leukemia (ALL) is a malignancy of the blood and bone marrow affecting both adults and children. Despite significant advancements in the treatment of ALL, its etiology remains multifactorial and complex. […] The etiology of Acute Lymphoblastic Leukemia remains a complex puzzle, tightly intertwined with a combination of genetic, environmental, and lifestyle factors. While significant progress has been made in identifying key genetic alterations and environmental exposures associated with ALL, further research is essential to understand the intricate interplay between genetic predispositions and environmental triggers. Improved understanding of the causes of ALL will aid in developing effective preventive strategies, targeted therapies, and personalized treatment approaches, ultimately reducing the burden of this devastating disease.

• #52 A causal mechanism for childhood acute lymphoblastic leukaemia | Nature Reviews Cancer

  https://www.nature.com/articles/s41568-018-0015-6

  Risk is further modified by inherited genetics, chance and, probably, diet. […] Childhood ALL can be viewed as a paradoxical consequence of progress in modern societies, where behavioural changes have restrained early microbial exposure. […] This engenders an evolutionary mismatch between historical adaptations of the immune system and contemporary lifestyles. […] Childhood ALL may be a preventable cancer.

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