ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib |
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| Authors: | Vivona Douglas Bueno Carolina T Lima Luciene T Hirata Rosario D C Hirata Mario H Luchessi André D Zanichelli Maria A Chiattone Carlos S Guerra-Shinohara Elvira M |
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| Institution: | 1. Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA;2. Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;3. Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA;4. Center for Genomics & Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA;5. Department of Medicine, Division of Nephrology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA;6. Department of Medicine, Division of Nephrology, Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota, USA;7. Minneapolis Medical Research Foundation, Minneapolis, Minnesota, USA;8. Department of Medicine, Renal Division, Emory University School of Medicine, Atlanta, Georgia, USA;9. General Surgery & HLA Immunogenetics Lab, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA;10. Alabama Regional Histocompatibility Laboratory at UAB, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA;11. Department of Pathology & Lab Medicine; Emory School of Medicine, Atlanta, Georgia, USA;12. Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA;13. Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA |
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| Abstract: | BackgroundImatinib 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 bioavailability. 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.AimTo investigate the relationship of ABCB1 polymorphisms with markers of response to IM in patients with CML.MethodsOne 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.ResultsABCB1 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).ConclusionsThe ABCB1 1236CT/2677GT/3435CT haplotype is positively associated with the major molecular response to IM in CML patients. |
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