Background Glutathione S‐transferases (GSTs) polymorphisms may impact on chronic myeloid leukemia (CML) risk or heterogeneous responses to Imatinib mesylate (IM). The aim of this study was to evaluate the correlation between GSTs polymorphisms and CML risk, treatment response. Methods We genotyped GSTM1, GSTT1 null deletion polymorphisms, and GSTP1 Ile105Val polymorphism by PCR methods and BCR‐ABL transcripts were analyzed by qRT‐PCR in 104 CML patients and 104 sex‐ and age‐matched healthy individuals. Results Individual analysis showed significant association of GSTM1 ( p = 0.008; OR = 0.46; 95% CI: 0.26–0.82) and GSTP1 genes ( p = 0.04; OR = 1.56; 95% CI: 1.016–2.423) with CML risk. The combined analysis indicated that GSTM1 null/GSTT1 present, GSTM1‐null/GSTP1M*(AG/GG) as well as GSTT1 present/ GSTP1M* genotype were associated with CML risk (ORg(‐):2.28; 95% CI: 1.29–4.04; ORgg: 2.85; 95% CI: 1.36–5.97; OR(‐)g: 1.75; 95% CI: 0.99–3.06, respectively). The proportion of CML cancer attributable to the interaction of smoking and GSTM1 null, GSTT1null, and GSTP1 M* was 42%, 39%, and 13%, respectively. Patients with GSTM1‐null and GSTP1 AG/GG genotype had significantly a lower rate of MMR achievement ( p = 0.00; p = 0.009 respectively). Event‐free survival (EFS) percentage was similar between GSTM1 null and GSTM1 present patients ( p = 0.21). Conclusion Our study suggests the influence of GSTM1 and GSTP1 polymorphisms on CML risk and treatment response. The interaction between GSTs polymorphisms and smoking plays a significant role on CML susceptibility.

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Mutations of the BCR-ABL1 kinase domain seem to be the most common cause of imatinib mesylate resistance in chronic myeloid leukemia (CML). We screened BCR-ABL1 kinase domain mutations using nested reverse transcriptase polymerase chain reaction and direct sequencing in 30 CML patients including 22 resistant patients and 8 patients with optimal response to imatinib. Three mutations of two different types were identified in 3 of 22 (13.6%) resistant patients. Two patients had p.E355G mutation in the catalytic domain, and the third patient had p.G398R in the activation loop that is reported here for the first time. No mutation was found in patients with optimal response to imatinib. The frequency of mutations was similar in patients with primary resistance compared with patients with secondary resistance (25 vs 11%; P=1). Mutation status had no impact on the overall survival and progression-free survival. p.E355G mutation was correlated with shorter survival (P=0.047) in resistant patients. We conclude that BCR- ABL1 mutations are associated with the clinical resistance, but may not be considered the only cause of resistance to imatinib. Mutational analysis may identify resistant patients at risk of disease progression.