Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib

Full text
Author(s):
Vivona, Douglas [1] ; Bueno, Carolina T. [1] ; Lima, Luciene T. [1] ; Hirata, Rosario D. C. [1] ; Hirata, Mario H. [1] ; Luchessi, Andre D. [1] ; Zanichelli, Maria A. [2] ; Chiattone, Carlos S. [3] ; Guerra-Shinohara, Elvira M. [1]
Total Authors: 9
Affiliation:
[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, BR-05508900 Sao Paulo - Brazil
[2] Hosp Brigadeiro, Serv Hematol, Sao Paulo - Brazil
[3] Santa Casa Sao Paulo, Dept Hematol & Hemoterapia, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: BLOOD CELLS MOLECULES AND DISEASES; v. 48, n. 2, p. 132-136, FEB 15 2012.
Web of Science Citations: 23
Abstract

Background: Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor used for treating chronic myeloid leukemia (CML). IM has high efficacy, however some individuals develop a resistance due to impaired bio-availability. Polymorphisms in genes encoding membrane transporters such as ABCB1 have been associated with differences in protein expression and function that influence the response to several drugs. Aim: To investigate the relationship of ABCB1 polymorphisms with markers of response to IM in patients with CML Methods: One hundred eighteen CML patients initially treated with a standard dose of IM (400 mg/day) for 18 months were selected at two health centers in Sao Paulo City, Brazil. The response criteria were based on the European LeukemiaNet recommendations. ABCB1 polymorphisms c.1236C>T (rs1128503), c.3435C>T (rs1045642) and c.2677G>T/A (rs2032582) were evaluated by PCR-RFLP. Results: ABCB1 polymorphisms were not related with a risk for CML in this sample population (p<0.05). In the CML group, frequencies of ABCB1 SNPs were similar between responder and non-responder patients (p>0.05). In the responder group, the frequency of ABCB11236CT/2677GT/3435CT haplotype was higher in patients with major molecular response (MMR) (51.7%) than in patients without MMR (8.3%, p = 0.010). Furthermore, carriers of this haplotype had increased the probability of reaching the MMR compared with the non-carriers (OR: 11.8; 95% CI: 1.43-97.3, p = 0.022). Conclusions: The ABCB1 1236CT/2677GT/3435CT haplotype is positively associated with the major molecular response to IM in CML patients. (C) 2011 Elsevier Inc. All rights reserved. (AU)