Activated FLT3 Receptor Tyrosine Kinase as a Therapeutic Target In Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous neoplastic disease characterized by deregulated proliferation of myeloid precursor cells combined with an arrest in the differentiation process. The abnormal survival advantage of transformed immature myeloid precursors further contributes to a marked impairment of the functional maturation of the various myeloid cell lineages. Intensive studies over the past 20 yr have resulted in the identification of leukemia-specific cytogenetic abnormalities, which provided considerable insight into the underlying pathogenesis of AML. This has also resulted in the prognostic stratification of AML patients into three different risk groups: those with favorable, intermediate or standard, and poor risk disease. Patients with favorable cytogenetics, i.e., those with translocations t(15;17), t(8;21), and inversion inv(16), have particularly benefited from an improved understanding of the molecular pathology of their disease, which has resulted in the identification of potential therapeutic targets. For example, the addition of all-trans retinoic acid during induction chemotherapy for acute promyelocytic leukemia (APL) patients with the PML/RARα (promyelocytic leukemia/retinoic acid receptor-α) fusion gene in t(15;17) has increased the 5-yr survival a further 20-30% compared with chemotherapy alone (1,2). [ABSTRACT FROM AUTHOR]