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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: BLOOD CELLS MOLECULES AND DISEASES; v. 48, n. 2, p. 132-136, FEB 15 2012.
• Citações Web of Science: 23

Resumo

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)

• Processo FAPESP: 09/54184-0 - Estudo da expressao de transportadores de membrana e sua relacao com marcadores de resposta ao mesilato de imatinibe em pacientes com leucemia mieloide cronica.
• Beneficiário: Elvira Maria Guerra Shinohara
• Modalidade de apoio: Auxílio à Pesquisa - Regular