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Updated: Mar 23, 2026

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Single nucleotide polymorphisms in apoptosis pathway are associated with response to imatinib therapy in chronic

Qiaoli Zheng1,2, Jiang Cao3, Nada Hamad4,5

  • 1Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

Journal of Translational Medicine
|March 25, 2016
PubMed
Abstract

Insights

Genetic variations in the Fas gene (rs2234767) may predict imatinib response in CML patients. This specific FAS genotype is linked to achieving deeper molecular response (MR4.5) more effectively.

Area of Science:

  • Pharmacogenomics
  • Molecular Biology
  • Oncology

Background:

  • Imatinib therapy for chronic myeloid leukemia (CML) relies on the Fas-mediated apoptosis pathway.
  • Inter-individual differences in apoptosis pathways may influence imatinib efficacy or resistance.

Purpose of the Study:

  • To investigate the association between genetic variations in apoptosis-related genes and imatinib treatment outcomes in Korean CML patients.
  • To identify potential genetic markers for predicting molecular response to imatinib therapy.

Main Methods:

  • Genotyping of eight single nucleotide polymorphisms (SNPs) in FAS, FASLG, CASP10, and APAF1 genes.
  • Analysis of the association between these genotypes and achieving molecular response with 4.5 log reduction (MR4.5) in 187 Korean CML patients.

Main Results:

  • The GG/GA genotype of FAS (rs2234767) was associated with a significantly higher rate of MR4.5 compared to the AA genotype (59.7% vs. 37.4% at 5 years, p=0.013).
  • Internal validation confirmed FAS (rs2234767) as a significant correlate of MR4.5 (p=0.050).
  • Multivariate analysis identified the FAS genotype (rs2234767) as an independent predictor of MR4.5 (p=0.019, Hazard Ratio=0.43).

Conclusions:

  • The Fas/FasL signaling pathway is crucial for imatinib-induced apoptosis in CML.
  • Specific single nucleotide polymorphism markers, particularly the FAS genotype (rs2234767), may serve as valuable surrogates for predicting deeper molecular responses following imatinib treatment.
Keywords:
Apoptosis pathwayChronic myeloid leukemiaImatinibSingle nucleotide polymorphisms

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