ATP-binding-cassette transporters in hematopoietic stem cells and their utility as therapeutical targets in acute and chronic myeloid leukemia.
ATP-binding-cassette (ABC) transporters are evolutionary extremely well-conserved transmembrane proteins that are highly expressed in hematopoietic stem cells (HSCs). The physiological function in human stem cells is believed to be protection against genetic damage caused by both environmental and naturally occurring xenobiotics. Additionally, ABC transporters have been implicated in the maintenance of quiescence and cell fate decisions of stem cells. These physiological roles suggest a potential role in the pathogenesis and biology of stem cell-derived hematological malignancies such as acute and chronic myeloid leukemia. This paper reviews the (patho)physiological role of ABC transporters in human normal and malignant HSCs and discusses its implications for their utility as therapeutical targets to eradicate leukemic stem cells in these diseases.
Raaijmakers
M H G P
MH
Department of Hematology, University Medical Center Nijmegen St. Radboud, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands. hraaijmakers@partners.com
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001549:Benzamides; D002454:Cell Differentiation; D019008:Drug Resistance, Neoplasm; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010641:Phenotype; D010879:Piperazines / Q000494:pharmacology; D011485:Protein Binding; D011743:Pyrimidines / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D000255:Adenosine Triphosphate