MOLECULAR-GENETICS OF CHILDHOOD LEUKEMIAS

Purpose: This review summarizes the molecular genetics of childhood le ukemias, with emphasis on pathogenesis and clinical applications. Desi gn: We first describe the most common genetic events that occur in ped iatric acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML ), and chronic myeloid leukemia (CML). We then illustrate how these mo lecular alterations may be used to alter therapy. Results: In childhoo d ALL, the TEL-AML1 fusion and hyperdiploidy are both associated with excellent treatment outcomes and therefore identify patients who may b e candidates for less intensive therapy. In contrast, MLL gene rearran gements and the BCR-ABL fusion confer a poor prognosis; these patients map be best treated by allogeneic bone marrow transplantation in firs t remission. Conclusions: Although clinical features are important pro gnostic indicators, genetic alterations of leukemic blasts may be bett er predictors of outcome for acute leukemia patients. We therefore fav or risk-adapted therapy based on classification schemes that incorpora te both genetic and clinical features.