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Single nucleotide polymorphisms in apoptosis pathway are associated with response to imatinib therapy in chronic myeloid leukemia.
- Source :
- Journal of Translational Medicine; 3/24/2016, Vol. 14, p1-11, 11p
- Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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]).<bold>Conclusions: </bold>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]
- Subjects :
- 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
RESEARCH evaluation
CHRONIC myeloid leukemia
TREATMENT effectiveness
GENOTYPES
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 14
- Database :
- Complementary Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 114027343
- Full Text :
- https://doi.org/10.1186/s12967-016-0837-5