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Molecules 2018, 23(1), 119; https://doi.org/10.3390/molecules23010119

Towards Comprehension of the ABCB1/P-Glycoprotein Role in Chronic Myeloid Leukemia

1
Laboratório de Hemato-Oncologia Celular e Molecular and Programa de Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Praça da Cruz Vermelha, 23, 6° andar, CEP 20230-130 Rio de Janeiro, Brazil
2
Laboratório de Imunologia Tumoral, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Av. Carlos Chagas Filho, 373, Cidade Universitária, CEP 21941-902 Rio de Janeiro, Brazil
*
Author to whom correspondence should be addressed.
Received: 21 November 2017 / Revised: 25 December 2017 / Accepted: 5 January 2018 / Published: 7 January 2018
(This article belongs to the Special Issue Counteracting Drug Resistant Mechanisms in Cancer)
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Abstract

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. View Full-Text
Keywords: chronic myeloid leukemia; P-glycoprotein; tyrosine kinase inhibitor; drug resistance; microvesicles; inhibitor apoptosis proteins; microRNAs; new compounds chronic myeloid leukemia; P-glycoprotein; tyrosine kinase inhibitor; drug resistance; microvesicles; inhibitor apoptosis proteins; microRNAs; new compounds
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Maia, R.C.; Vasconcelos, F.C.; Souza, P.S.; Rumjanek, V.M. Towards Comprehension of the ABCB1/P-Glycoprotein Role in Chronic Myeloid Leukemia. Molecules 2018, 23, 119.

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