to play a significant role. Aside from the KMT2A rearrangement, only one extra mutation is typically found. Environmental exposures are not needed to help create more mutations. Risk factors Genetics Common inherited risk factors include mutations in ARID5B, CDKN2A/2B, CEBPE, IKZF1, GATA3, PIP4K2A and, more rarely, TP53. These genes play important roles in cellular development, proliferation, and differentiation. Individually, most of these mutations are low risk for ALL. Significant risk of disease occurs when a person inherits several of these mutations together. The uneven distribution of genetic risk factors may help explain differences in disease rates among ethnic groups. For instance, the ARID5B mutation is less common in ethnic African populations. Several genetic syndrome also carry increased risk of ALL. These include: Down syndrome, Fanconi anemia, Bloom syndrome, X-linked agammaglobulinemia, severe combined immunodeficiency, Shwachman–Diamond syndrome, Kostmann syndrome, neurofibromatosis type 1, ataxia-telangiectasia, paroxysmal nocturnal hemoglobinuria, and Li–Fraumeni syndrome. Fewer than 5% of cases are associated with a known genetic syndrome. Rare mutations in ETV6 and PAX5 are associated with a familial form of ALL with autosomal dominant patterns of inheritance. Environmental The environmental exposures that contribute to emergence of ALL is contentious and a subject of ongoing debate. High levels of radiation exposure from nuclear fallout is a known risk factor for developing leukemia. Evidence whether lesser radiation, as from x-ray imaging during pregnancy, increases risk of disease remains inconclusive. Studies that have identified an association between x-ray imaging during pregnancy and ALL found only a slightly increased risk. Exposure to strong electromagnetic radiation from power lines has also been associated with a slightly increased risk of ALL. This result is questioned as no causal mechanism linking electromagnetic radiation with cancer is known. High birth weight (greater than 4000 g or 8.8 lbs) is also associated with a small increased risk. The mechanism connecting high birth weight to ALL is also not known. Evidence suggests that secondary leukemia can develop in individuals treated with certain types of chemotherapy, such as epipodophyllotoxins and cyclophosphamide. Infections 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. Delayed development of the immune system due to limited disease exposure may result in excessive production of lymphocytes and increased mutation rate during an illness. Several studies have