دورية أكاديمية
أعرض في EDS

ABCB1 haplotypes are associated with P-gp activity and affect a major molecular response in chronic myeloid leukemia patients treated with a standard dose of imatinib.

التفاصيل البيبلوغرافية
العنوان: ABCB1 haplotypes are associated with P-gp activity and affect a major molecular response in chronic myeloid leukemia patients treated with a standard dose of imatinib.
المؤلفون: Vivona D; Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Science, University of São Paulo, São Paulo 05508-900, Brazil., Lima LT; Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Science, University of São Paulo, São Paulo 05508-900, Brazil., Rodrigues AC; Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo 05508-900, Brazil., Bueno CT; Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Science, University of São Paulo, São Paulo 05508-900, Brazil., Alcantara GK; Department of Clinical, Toxicological and Bromatological Analyses, Faculty of Pharmaceutical Science, University of São Paulo, Ribeirão Preto 14040-903, Brazil., Barros LS; Department of Clinical, Toxicological and Bromatological Analyses, Faculty of Pharmaceutical Science, University of São Paulo, Ribeirão Preto 14040-903, Brazil., DE Moraes Hungria VT; Department of Hematology and Hemotherapy, Santa Casa Medical School, São Paulo 01223-001, Brazil., Chiattone CS; Department of Hematology and Hemotherapy, Santa Casa Medical School, São Paulo 01223-001, Brazil., DE Lourdes Lopes Ferrari Chauffaille M; Department of Clinical and Experimental Oncology, Federal University of São Paulo, São Paulo 04023-900, Brazil., Guerra-Shinohara EM; Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Science, University of São Paulo, São Paulo 05508-900, Brazil.
المصدر: Oncology letters [Oncol Lett] 2014 Apr; Vol. 7 (4), pp. 1313-1319. Date of Electronic Publication: 2014 Feb 07.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Spandidos Publications] Country of Publication: Greece NLM ID: 101531236 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1792-1074 (Print) Linking ISSN: 17921074 NLM ISO Abbreviation: Oncol Lett Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Athens : Spandidos Publications]
مستخلص: Despite the high efficacy of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) patients, some individuals develop resistance due to impaired bioavailability. It has been previously demonstrated that the haplotypes for ATP-binding cassette subfamily B member 1 ( ABCB1 )with c.1236C>T, c.3435C>T and c.2677G>T/A polymorphisms markedly affect the secondary structure of ABCB1 mRNA and its activity. These modifications may affect efflux transporter activity and response to treatment with IM. The aim of the present study was to investigate the influence of ABCB1 haplotypes on P-glycoprotein (P-gp) activity, IM plasma levels and IM response. In total, 28 chronic-phase CML patients treated with a standard dose of IM (400 mg/day) were studied. The patients were selected according to the haplotypes of ABCB1, with c.1236C>T, c.3435C>T and c.2677G>T polymorphisms, and were classified into two groups based on the presence of the mutated allele in each genotype for the three ABCB1 polymorphisms. In addition, expression of P-gp and breakpoint cluster region-abelson 1 (BCR-ABL1), ABCB1 and solute carrier family 22 member 1 (SLC22A1) mRNA were evaluated. The P-gp activity in the wild-type group was found to be higher than that in the mutated group (59.1 vs. 38.3%; P=0.001). Furthermore, the patients who did not achieve major molecular response (MMR) showed a higher rate of efflux mediated by P-gp when compared with individuals who achieved MMR (64.7 vs. 45.7%; P=0.001). All patients without MMR demonstrated effluxes of >60%. In addition, patients without MMR exhibited lower plasma concentrations of IM compared with those with MMR (0.51 vs. 1.42 μg/ml; P=0.001). Higher levels of SLC22A1 mRNA were observed in patients who achieved MMR and complete molecular response (P<0.05). In conclusion, the ABCB1 1236CT/3435CT/2677GT and 1236TT/3435TT/2677TT haplotypes are associated with reduced P-gp activity and MMR in chronic-phase CML patients treated with a standard dose of IM.
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فهرسة مساهمة: Keywords: ABCB1; chronic myeloid leukemia; imatinib mesylate
تواريخ الأحداث: Date Created: 20140325 Latest Revision: 20220408
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3961201
DOI: 10.3892/ol.2014.1857
PMID: 24660038
قاعدة البيانات: MEDLINE
الوصف
تدمد:1792-1074
DOI:10.3892/ol.2014.1857