ABCB1 polymorphisms predict imatinib response in chronic myeloid leukemia patients: a systematic review and meta-analysis

作者：Zheng, Q.; Wu, H.; Yu, Q.; Kim, D. H.; Lipton, J. H.; Angelini, S.; Soverini, S.; Vivona, D.; Takahashi, N.; Cao, J.^*

来源：The Pharmacogenomics Journal, 2015, 15(2): 127-134.

DOI：10.1038/tpj.2014.54

• MAJOR MOLECULAR RESPONSE
• GENE MDR1 POLYMORPHISMS
• TRANSPORTER POLYMORPHISMS
• CLINICAL-RESPONSE
• RESISTANCE
• PHARMACOKINETICS
• ASSOCIATION
• INHIBITORS
• THERAPY
• BCR

Imatinib mesylate, a competitive tyrosine kinase inhibitor, is considered the first-line therapy drug for Ph+ chronic myeloid leukemia (CML). Three single-nucleotide polymorphisms (SNPs) in the ATP-binding cassette, subfamily B (MDR/TAP), member 1 gene (ABCB1/MDR1), c.1236C>T, c.2677G>T/A and c.3435C>T, have been shown to affect cellular transport/metabolism of imatinib. The associations between these SNPs and imatinib response in CML patients have been widely evaluated, but the results were inconsistent. To derive a conclusive assessment of the associations, we performed a meta-analysis by combining data from a total of 12 reports including 1826 patients. The results showed that the 2677G allele or 3435T allele predicted a worse response to imatinib in CML patients, whereas 1236CC genotype was associated with better response in CML patients from Asian region. In conclusion, this meta-analysis suggests that c.1236C>T, c.2677G>T/A and c.3435C>T can be served as predictive markers for the therapeutical use of imatinib in CML patients.

• 出版日期2015-4
• 单位浙江大学