GROWTH FACTOR-MEDIATED TERMINAL DIFFERENTIATION OF CHRONIC MYELOID-LEUKEMIA

Expression of the BCR-ABL chimeric gene in chronic myeloid leukemia re sults in the inhibition of apoptosis, a genetically programmed process of autonomous cell death. BCR-ABL and other genetic factors that supp ress apoptosis confer cross-resistance to cytotoxic agents with divers e mechanisms of action. Eradication of the chronic myeloid leukemia cl one requires strategies that circumvent this inherent resistance to cy totoxic therapy. We have determined that BCR-ABL expression augments t he sensitivity of hematopoietic cells to growth factor-mediated signal s of differentiation; hematopoietic growth factors induce the selectiv e terminal differentiation of chronic myeloid leukemia progenitors at concentrations that allow optimal growth of normal progenitors. Hemato poietic growth factors may be an effective strategy for the eliminatio n of cytotoxic therapy-resistant Leukemic cells by inducing their term inal differentiation while allowing concomitant expansion of coexisten t normal hematopoietic progenitors.