Acute lymphoblastic leukemia (ALL) is a biologically diverse malignancy in terms of cellular origins, chromosome abnormalities, and mutations. This heterogeneity has important implications for differential diagnosis, choice of therapy, and prognosis and etiology. New diagnostic methods have been developed that enable cell type/lineage and abnormal genotype to be identified in individual non-dividing cells. Acute leukemia is likely to involve a minimum of two mutations, and recent studies on identical twins with leukemia suggest that for pediatric ALL, the first mutation occurs in utero. Postnatal events are also critical and recent epidemiological evidence suggests that these may involve an abormal response to infection.
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