Leukemia and ABC transporters

Acute myeloid leukemia (AML) is a heterogeneous disease caused by aberrant proliferation and/or differentiation of myeloid progenitors. However, only ~65% of AML patients respond to induction chemotherapy and the overall survival rate for AML remains low (~24% for 5-year survival). The conventional view suggests that ATP-binding cassette (ABC) transporters contribute to treatment failure due to their drug-effluxing capabilities. This might be overly simplistic. Some ABC transporters export endogenous substrates that have defined roles in normal hematopoietic progenitors. It is conceivable that these substances also provide an advantage to leukemic progenitors. This review will highlight how certain endogenous substrates impact normal hematopoietic cells and suggest that ABC transporters facilitate export of these substances to affect both normal hematopoietic and leukemic progenitors. For example, the ability to export certain endogenous ligands may facilitate leukemogenesis by modifying leukemic progenitor cell proliferation or survival. If so, the addition of ABC transporter inhibitors to traditional chemotherapy might improve therapeutic efficacy by not just increasing intracellular drug accumulation but also blocking the beneficial effects ABC transporter ligands have on cell survival.