ABC transporter expression in hematopoietic stem cells and the role in AML drug resistance.
ATP-binding cassette (ABC) transporters are known to play an important role in human physiology, toxicology, pharmacology, and numerous disorders including acute myeloid leukemia (AML). In AML only a few cells have properties allowing for ongoing proliferation and for expansion of this malignant disorder. These very primitive cells, referred to as leukemic stem cells, reside mostly in a quiescent cell cycle state. These cells have the capacity of self-renewal and are likely characterized by a high expression of a number of ABC transporters. In addition, over-expression of certain ABC transporters in leukemic cells has been associated with poor treatment outcome in AML patients. Therefore, to be able to improve diagnostics and therapies for AML patients, it may be important to better characterize this quiescent stem cell population. Particularly knowledge of the biology of highly expressed ABC transporters in these primitive leukemic cells might provide new insights to improve therapeutic options. This review provides an overview about ABC transporters and AML in general and particularly of the ABC transporters involved in multidrug resistance and cholesterol metabolism in primitive normal and leukemic cells.
de Jonge-Peeters
Susan D P W M
SD
Department of Hematology, University of Groningen and University Medical Center Groningen, P.O. Box 30.001, Groningen 9700 RB, The Netherlands.
Kuipers
Folkert
F
de Vries
Elisabeth G E
EG
Vellenga
Edo
E
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000208:Acute Disease; D002784:Cholesterol / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol