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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 [J Transl Med] 2016 Mar 24; Vol. 14, pp. 82. Date of Electronic Publication: 2016 Mar 24. - Publication Year :
- 2016
-
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.<br />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.<br />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]).<br />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.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Child
Demography
Female
Genotype
Humans
Imatinib Mesylate pharmacology
Male
Middle Aged
Multivariate Analysis
Prognosis
Reproducibility of Results
Treatment Outcome
Young Adult
Apoptosis genetics
Imatinib Mesylate therapeutic use
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Polymorphism, Single Nucleotide genetics
Signal Transduction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1479-5876
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- Journal of translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 27009330
- Full Text :
- https://doi.org/10.1186/s12967-016-0837-5