Frequency of T315I Mutation in Patients with Chronic Myeloid Leukemia Before and During Imatinib Treatment: A Study in North-East of Iran

Abstract

Background and Objective: Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by an aberrant BCR-ABL fusion protein. Imatinib mesylate (IM) is a tyrosine kinase inhibitor that induces clinical remissions in chronic-phase CML patients. The T315I mutation at the gatekeeper residues of BCR-ABL confers resistance to both IM and second-generation TKIs, including dasatinib and nilotinib. Our objective was to determine the prevalence of T315I mutation between two groups of CML patients before and during Imatinib treatment in North-East of Iran.
Materials and Methods: This study was conducted on 100 newly diagnosed cases of CML (before commencing IM treatment) and 25 IM-resistant CML patients. PCR-RFLP, ASO-PCR, and direct sequencing were performed to detect T315I mutations.
Results: The median age of newly-diagnosed and IM-resistant patients was 48±14 and 50±12.3 years, respectively. Males/Females ratio was 1 and 1.08 for newly diagnosed and IM-resistant patients, respectively. There was no significant difference regarding the age and sex between the two groups. During the study, T315I mutational analysis was performed for all 125 patients. The prevalence of T315I mutation was 0% and 4% for newly-diagnosed and IM-resistant patients, respectively. T315I mutation was not detected before IM administration, although it was detected in 1 (4%) among resistant patients who were at least 6-months on IM treatment.
Conclusion: These observations suggest that T315I mutation may be categorized as secondary resistance and induce clonal expansion due to BCR/ABL instability. Hence, BCR-ABL mutations are less likely to appear before the onset of treatment, as presented in our study.

Keywords: T315I Mutation, Chronic Myeloid Leukemia (CML), Imatinib Resistance