Imatinib resistance mutation analysis: experience from a tertiary oncology center
Purpose: BCR-ABL kinase domain (KD) mutations account for 50-90% of the imatinib resistance observed in patients of CML-chronic phase. In CML-CP patients receiving imatinib first-line, mutation analysis is recommended in case of failure or suboptimal response using European LeukemiaNet (ELN) criteria. The present study was carried out at a tertiary oncology centre in south India to assess which mutations accounted for resistance to imatinib among patients of chronic phase CML being treated with imatinib.
Methods: This was a retrospective observational study. We analyzed patients who were tested for imatinib resistance mutation in view of suboptimal responses while on imatinib or imatinib failure. Direct sequencing of the BCR-ABL transcript by the Sanger method was used for IRMA testing.
Results: Out of 120 tested for IRMA, 36 (30%) had detectable mutations. We observed a higher frequency of mutations at amino acids T315, F359 and M351T.
Conclusions: Among the patients who were tested for imatinib resistance mutation in view of suboptimal responses while on imatinib or imatinib failure, 30% had IRMA +ve mutations. The high incidence of imatinib resistance in present study may be attributed to the fact that our patients were given higher dose of imatinib (600 mg), if they failed to achieve CCyR at 12 months or CHR at 3 months as they could not afford second generation TKIs.
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