Mutational analysis of T315I in patients with chronic myeloid leukemia who did not respond to second-generation tyrosine kinase inhibitors

Abstract

BACKGROUND: Chronic myelogenous leukemia (CML) is a hematological stem cell disorder that associates with mutations in BCR-ABL. Although mutations identified in more than 30 different amino acids, the highest degree of resistance was associated with single-point mutation T315I of the ABL gene. OBJECTIVES: This study aims to identify the prevalence of T315I mutation among CML patients who lost their Major molecular response to second-generation tyrosine kinase inhibitor (TKI) at the time of the study and its relation to failure response. SUBJECTS AND METHODS: A prospective cross-sectional study included 50 adult patients diagnosed with CML. We have used the Sanger sequencing polymerase chain reaction based methods for detection of T315I mutation. RESULTS: Out of 50 patients, 28 were female (56%). Patients' age was ranged between 23 and 63 years with a mean age of 42.8 ± 11.46 years. There was no expression of T315I mutation in any of 50 CML patients, however, there was another mutation have been detected which is rs2070997 (response to drug) and was positive in 18 patients. There were 8 (16%) patients that have rs2070997 mutation have primary failure on first-generation TKIs, while the other 10 (20%) patients were those who started second-generation TKIs directly. CONCLUSIONS: T315I mutation was not common in patients with CML-chronic phase. Other (BCR-ABL dependent or independent) mechanism could be responsible of TKIs resistance.

Keywords

• chronic myelogenous leukemia
• t315i mutation
• tyrosine kinase inhibitor resistance