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RSS FeedsMolecules, Vol. 23, Pages 119: Towards Comprehension of the ABCB1/P-Glycoprotein Role in Chronic Myeloid Leukemia (Molecules)


7 january 2018 12:45:28

Molecules, Vol. 23, Pages 119: Towards Comprehension of the ABCB1/P-Glycoprotein Role in Chronic Myeloid Leukemia (Molecules)

Abstract: The introduction of imatinib (IM), a BCR-ABL1 tyrosine kinase inhibitor (TKI), has represented a significant advance in the first-line treatment of chronic myeloid leukemia (CML). However, approximately 30% of patients need to discontinue IM due to resistance or intolerance to this drug. Both resistance and intolerance have also been observed in treatment with the second-generation TKIs--dasatinib, nilotinib, and bosutinib--and the third-generation TKI--ponatinib. The mechanisms of resistance to TKIs may be BCR-ABL1-dependent and/or BCR-ABL1-independent. Although the role of efflux pump P-glycoprotein (Pgp), codified by the ABCB1 gene, is unquestionable in drug resistance of many neoplasms, a longstanding question exists about whether Pgp has a firm implication in TKI resistance in the clinical scenario. The goal of this review is to offer an overview of ABCB1/Pgp expression/activity/polymorphisms in CML. Understanding how interactions, associations, or cooperation between Pgp and other molecules--such as inhibitor apoptosis proteins, microRNAs, or microvesicles--impact IM resistance risk may be critical in evaluating the response to TKIs in CML patients. In addition, new non-TKI compounds may be necessary in order to overcome the resistance mediated by Pgp in CML. Digg Facebook Google StumbleUpon Twitter
126 viewsCategory: Biochemistry, Chemistry, Molecular Biology
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