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 4000g or 8.8lbs) 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.
This information is particularly valuable for classification and can in part explain the different prognoses of these groups. In regards to genetic analysis, cases can be stratified according to ploidy, a number of sets of chromosomes in the cell, and specific genetic abnormalities, such as translocations. Hyperdiploid cells are defined as cells with more than 50 chromosomes, while hypodiploid are defined as cells with less than 44 chromosomes. Hyperdiploid cases tend to carry a good prognosis while hypodiploid cases do not. For example, the most common specific abnormality in childhood B-ALL is the t(12;21) ETV6–RUNX1 translocation, in which the RUNX1 gene, encoding a protein involved in transcriptional control of hemopoiesis, has been translocated and repressed by the ETV6–RUNX1 fusion protein.Below is a table with the frequencies of some cytogenetic translocations and molecular genetic abnormalities in ALL. Classification
French-American-British
Historically, prior to 2008, ALL was classified morphologically using the French-American-British (FAB) system that heavily relied on morphological assessment. The FAB system takes into account information on size, cytoplasm, nucleoli, basophilia (color of cytoplasm), and vacuolation (bubble-like properties). While some clinicians still use the FAB scheme to describe tumor cell appearance, much of this classification has been abandoned because of its limited impact on treatment choice and prognostic value. : 491 World Health Organization
In 2008, the World Health Organization classification of acute lymphoblastic leukemia was developed in an attempt to create a classification system that was more clinically relevant and could produce meaningful prognostic and treatment decisions.