title: Single nucleotide polymorphisms in apoptosis pathway are associated with response to imatinib therapy in chronic myeloid leukemia.
abstract: BACKGROUND
  The mechanism of action of imatinib is known to involve the Fas-mediated apoptosis pathway. Consequently inter-individual variations in this apoptosis pathway might be associated with imatinib response or resistance.
  
  
  METHODS
  This study attempted to focus on eight genotypes in the apoptosis pathway including FAS (rs1800682, rs2229521, rs2234767 and rs2234978), FASLG (rs763110), CASP10 (rs13006529), and APAF1 (rs1439123, rs2288713) and analyzed their association with treatment outcomes including molecular response with 4.5 log reduction (MR4.5), following imatinib therapy in 187 Korean CML patients.
  
  
  RESULTS
  The GG/GA genotype in FAS (rs2234767) showed a higher rate of MR4.5 than the AA genotype (at 5 years 59.7 vs 37.4 %, p = 0.013). Using a bootstrap procedure for internal validation we confirmed that FAS (rs2234767) correlates with MR4.5 (p = 0.050). Multivariate analysis confirmed that the FAS genotype (rs2234767) is an independent surrogate for MR4.5 (p = 0.019, HR 0.43, 95 % CI [0.22-0.87]).
  
  
  CONCLUSIONS
  The Fas/FasL signaling pathway may represent the major pathway that mediates apoptosis in CML treated with imatinib. SNP markers in the apoptosis pathway including FAS genotype (rs2234767) can be potential surrogates for predicting deeper molecular response after imatinib therapy.
authors.affiliation: Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.|Clinical Research Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Clinical Research Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, China. caoj@zju.edu.cn.
authors.forename: Jiang
authors.identifier: http://orcid.org/0000-0001-9542-5279
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Nada
authors.initials: N
authors.lastname: Hamad
authors.affiliation: Department of Hematology/Oncology, Chonnam National University Hwasun Hospital, Chonnam National University, Hwasun, South Korea.
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Hematology/Oncology, Kyungpook National University Hospital, Kyungpook National University, Daegu, South Korea.
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Department of Hematology/Oncology, Kyungpook National University Hospital, Kyungpook National University, Daegu, South Korea.
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. leukemia1@skku.edu.
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Dennis Dong Hwan
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D002648:Child; D003710:Demography; D005260:Female; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000068877:Imatinib Mesylate
keywords: Apoptosis pathway; Chronic myeloid leukemia; Imatinib; Single nucleotide polymorphisms