Frequency of T۳۱۵I Mutation in Patients with Chronic Myeloid Leukemia Before and During Imatinib Treatment: A Study in North-East of Iran

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 T۳۱۵I 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 T۳۱۵I 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 ۱۰۰ newly diagnosed cases of CML (before commencing IM treatment) and ۲۵ IM-resistant CML patients. PCR-RFLP, ASO-PCR, and direct sequencing were performed to detect T۳۱۵I mutations. Results: The median age of newly-diagnosed and IM-resistant patients was ۴۸±۱۴ and ۵۰±۱۲.۳ years, respectively. Males/Females ratio was ۱ and ۱.۰۸ 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, T۳۱۵I mutational analysis was performed for all ۱۲۵ patients. The prevalence of T۳۱۵I mutation was ۰% and ۴% for newly-diagnosed and IM-resistant patients, respectively. T۳۱۵I mutation was not detected before IM administration, although it was detected in ۱ (۴%) among resistant patients who were at least ۶-months on IM treatment. Conclusion: These observations suggest that T۳۱۵I 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:

T۳۱۵I Mutation , Chronic Myeloid Leukemia (CML) , Imatinib Resistance