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ABC转运蛋白在造血干细胞中的表达及其在急性髓系白血病耐药中的作用。

ABC transporter expression in hematopoietic stem cells and the role in AML drug resistance.

作者信息

de Jonge-Peeters Susan D P W M, Kuipers Folkert, de Vries Elisabeth G E, Vellenga Edo

机构信息

Department of Hematology, University of Groningen and University Medical Center Groningen, P.O. Box 30.001, Groningen 9700 RB, The Netherlands.

出版信息

Crit Rev Oncol Hematol. 2007 Jun;62(3):214-26. doi: 10.1016/j.critrevonc.2007.02.003. Epub 2007 Mar 23.

Abstract

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.

摘要

已知ATP结合盒(ABC)转运蛋白在人体生理学、毒理学、药理学以及包括急性髓系白血病(AML)在内的多种疾病中发挥重要作用。在AML中,只有少数细胞具有持续增殖和扩展这种恶性疾病的特性。这些非常原始的细胞,即白血病干细胞,大多处于静止细胞周期状态。这些细胞具有自我更新能力,并且可能具有多种ABC转运蛋白的高表达特征。此外,白血病细胞中某些ABC转运蛋白的过表达与AML患者的不良治疗结果相关。因此,为了能够改善AML患者的诊断和治疗,更好地表征这种静止干细胞群体可能很重要。特别是了解这些原始白血病细胞中高表达的ABC转运蛋白的生物学特性,可能会为改善治疗选择提供新的见解。本综述概述了ABC转运蛋白和AML的一般情况,特别是涉及原始正常细胞和白血病细胞多药耐药性和胆固醇代谢的ABC转运蛋白。

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