1. Single nucleotide polymorphisms in apoptosis pathway are associated with response to imatinib therapy in chronic myeloid leukemia.
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Qiaoli Zheng, Jiang Cao, Hamad, Nada, Hyeoung-Joon Kim, Joon Ho Moon, Sang Kyun Sohn, Chul Won Jung, Lipton, Jeffrey H., Dong Hwan Kim, Dennis, Zheng, Qiaoli, Cao, Jiang, Kim, Hyeoung-Joon, Moon, Joon Ho, Sohn, Sang Kyun, Jung, Chul Won, and Kim, Dennis Dong Hwan
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SINGLE nucleotide polymorphisms , *APOPTOSIS , *DRUG therapy , *IMATINIB , *TREATMENT of chronic myeloid leukemia , *ANTINEOPLASTIC agents , *CELLULAR signal transduction , *DEMOGRAPHY , *FUNCTIONAL assessment , *GENETIC polymorphisms , *MULTIVARIATE analysis , *PROGNOSIS , *CHRONIC myeloid leukemia , *TREATMENT effectiveness , *GENOTYPES ,RESEARCH evaluation - 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. [ABSTRACT FROM AUTHOR]- Published
- 2016
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