title: ABCB1 polymorphisms predict imatinib response in chronic myeloid leukemia patients: a systematic review and meta-analysis.
abstract: 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.
authors.affiliation: Clinical Research Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Chronic Myelogenous Leukemia Group, Princess Margaret Cancer Centre, University Health Network University of Toronto, Toronto, Ontario, Canada.
authors.forename: D H Dennis
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Chronic Myelogenous Leukemia Group, Princess Margaret Cancer Centre, University Health Network University of Toronto, Toronto, Ontario, Canada.
authors.forename: J H
authors.initials: JH
authors.lastname: Lipton
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Angelini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology, University of Bologna, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Soverini
authors.affiliation: Departmento de Análises Clínicas e Toxicológicas da Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: D
authors.initials: D
authors.lastname: Vivona
authors.affiliation: Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Clinical Research Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Cao
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate