title: Trough concentration and ABCG2 polymorphism are better to predict imatinib response in chronic myeloid leukemia: a meta-analysis.
abstract: OBJECTIVE
  The present study aimed to conduct a series of meta-analyses to investigate the influence of imatinib trough concentration (C0), as well as ABCB1 and ABCG2 polymorphisms, on the clinical response in patients with chronic myeloid leukemia (CML).
  
  
  METHODS
  A literature search was conducted using the PubMed and Cochrane electronic databases to locate relevant papers from 2003 onward. Then, an initial meta-analysis of 14 studies involving 2184 patients was conducted to understand the effect of imatinib mesylate (IM) C0on clinical outcome in CML patients. Subsequently, a series of meta-analyses were performed, including up to 23 studies with 2577 patients, on the effect of genetic polymorphisms of ABCB1 and ABCG2 on the clinical response to IM.
  
  
  RESULTS
  Meta-analysis revealed that patients who achieved a major molecular response (MMR) have a significantly higher IM C0than those who failed to achieve an MMR. We also found that the patients who achieved a complete cytogenic response (CCyR) have a significantly higher IM C0than those who did not achieve a CCyR. However, no significant difference in IM C0was found between the complete molecular response and non-complete molecular response groups. Additional analysis showed that ABCG2 421 variant A allele was significantly associated with a higher rate of MMR and overall response, especially in Asian patients. Meta-analysis did not reveal a correlation between ABCB1 C3435T and C1236T polymorphisms with any clinical response to IM. However, the G2677T/A polymorphism could play a role in IM response in the recessive model.
  
  
  CONCLUSIONS
  This meta-analysis demonstrates that there was a significant correlation between the IM trough concentration and clinical responses, especially MMR and CCyR, in CML patients. Furthermore, we found that the probability of successful treatment was correlated with the ABCG2 C421A polymorphism, at least within the Asian population. We failed to determine an association between ABCB1 polymorphisms and IM response, although the G2677T/A polymorphism might be involved. However, further large-scale investigations using more sensitive genotyping methods would be required to confirm this.
authors.affiliation: Laboratory of Clinical Pharmacology, Department of Hematology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan Province 410008, People's Republic of China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Jiang
authors.affiliation: Laboratory of Clinical Pharmacology, Department of Hematology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan Province 410008, People's Republic of China.
authors.forename: Xie-Lan
authors.initials: XL
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Nephrology, & Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita city, Akita 010-8543, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Pharmacology, University of Bologna, Bologna 40126, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Angelini
authors.affiliation: Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry 605 006, India.
authors.forename: Biswajit
authors.initials: B
authors.lastname: Dubashi
authors.affiliation: Clinical Pharmacy & Pharmacology Research Institute, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan Province 410011, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Clinical Pharmacy & Pharmacology Research Institute, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan Province 410011, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects / Q000235:genetics*; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D000068877:Imatinib Mesylate
keywords: ABCB1; ABCG2; clinical response; imatinib; meta-analysis; polymorphism; trough concentration