title: Leukemia and ABC transporters.
abstract: 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.
authors: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Yu
authors: Y
authors: Fukuda
authors: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Shangli
authors: S
authors: Lian
authors: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. Electronic address: john.schuetz@stjude.org.
authors: John D
authors: JD
authors: Schuetz
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001692:Biological Transport / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D051379:Mice; D017211:Treatment Failure
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents
keywords: ABC transporter; AML; Leukotriene; PGE(2); Porphyrin
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