Molecular screening for e255k mutations in imatinib resistant-cml

Saba Yari,1 Reza masoumi,2,* Mehrdad payandeh,3 Kheirollah yari,4

1. Department of Biology, Faculty of Science, University of Maragheh, Marāgheh, Iran.
2. Department of Biology, Faculty of Science, University of Maragheh, Marāgheh, Iran.
3. Department of Hematology and Medical Oncology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
4. Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Abstract

Introduction

Chronic myelogenous leukemia (cml) is a clonal disease that kind of hematopoietic stem-cell cancer. a significant number of cml patients who do not achieve an adequate response to to first generation of tyrosine kinase inhibitor imatinib mesylate (im). resistance to the imatinib in bcr/abl-positive leukemias is typically associated with mutations in the kinase domain of bcr/abl, which include mutation e255k. the aim of this study is to evaluate the frequency of e255k mutation in cml patients who showed criteria of failure response to imatinib by using rt-pcr-rflp.

Methods

This study was performed on 20 cml patients with imatinib resistance, who referred to hospital of kermanshah city, between september 2016 to july 2017. the mean age of patients was 50 (31-83) years, 9 were male and 11 female. to identify e255k mutation in this patient the rna extracted from peripheral blood of patient and molecular screening for the presence of e255k mutation was performed by rt-pcr and then restriction fragment length polymorphism (rflp) was performed.

Results

The result of molecular screening showed that two of the cml patients were positive for e255k mutation and other cml patients were negative for this mutation.

Conclusion

We conclude that the presence of another types of point mutations or other mechanisms for resistance to could be the causes of im resistance. so identification cause of resistance may be useful for improving therapeutic strategies, avoiding delay in treatment and excessive expenditure in cml patients with imatinib resistance.

Keywords

Chronic myeloid leukemia; imatinib resistance; e255k mutation; rt- pcr; rflp