Analysis of Prevalence and Accumulation of Mutations Associated With Imatinib Based Therapy in Chronic Myeloid Leukemia Patients

Ratan J. Lihite, Nityanand Bolshette, Mangala Lahkar, Pabitra Kumar Gogoi, Pradeep Kumar Patnana

Abstract


AIM: To identify accumulation of mutations in CML patients with chronic phase at ABL kinase codon 253 and 315 after the course of imatinib therapy for 12 months with respect to clinical outcome.

METHODS: In this cross sectional study, 103 CML patients with chronic phase attended between January 2013 and December 2014 at Gauhati Medical College & Hospital, Guwahati, Northeast India were enrolled. Peripheral blood samples were collected from CML patients who were on imatinib therapy for ABL kinase domain mutational analysis and again after 12 months, blood samples were obtained for mutational analysis to determine any accumulation of mutations in ABL kinase domain by RFLP method with mutation-specific restriction enzymes. Sokal scores were determined at the time of enrolment of CML patients and adverse effects to imatinib therapy were also documented.

RESULTS: The median age at the time of enrolment of CML patients was 49.50 (45-56). Five patients (4.8%) were detected to have mutation at T315I after 12 months of imatinib therapy determined by mutation specific restriction digestion enzymes. Of these 5 patients, 2 patients were at high risk and other 3 patients were at intermediate risk as per sokal score. In our study, 425 adverse effects were reported to imatinib mesylate. Hypopigmentation was most commonly reported adverse effects to imatinib therapy. After one year of exposure to imatinib therapy, leukocytosis and thrombocytopenia were significantly found in CML patients with mutations. Hematologic and cytogenetic responses were significantly partial in CML patients with mutations.

CONCLUSION: In this study, 5 CML patients were reported to accumulate T315I mutations after 12 months of imatinib exposure and thus the prevalence of CML patients with mutation was 4.8%. Leukocytosis and thrombocytopenia were significantly reported in CML patients with mutations.


Keywords


CML; T315I; Imatinib; Mutations; ABL kinase

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