Association of T315I mutation with resistance to tyrosine kinase inhibitor therapy in patients with CML attended the Oncology-Hematology center in Al-Najaf city of Iraq

摘要

Background Notwithstanding the tremendous achievement of imatinib against BCR-ABL, development of primary or secondary resistance, most often because of point mutations in the BCR-ABL tyrosine kinase domain, is pretty commonplace. Among these mutations, the most frequent mutation, T315I mutation, is resistant to all presently registered BCR-ABL Tyrosine Kinase Inhibitors (TKIs) with the notable exception of ponatinib. Aims Evaluation the etiological association of T315I mutation with the failure or warning molecular responses of our chronic myeloid leukemia (CML) patients to Tyrosine Kinase Inhibitors (TKIs) in keeping to national and international guideline for molecular monitoring. Patients, materials and methods This was a retrospective observational case control study of CML patients who attended the Oncology-Hematology center in Al-Najaf city, performed during a period from April 2015 to April 2016. Medical information has been reviewed for treatment response and the outcomes of serial measurements of BCR-ABL transcripts levels through RT-qPCR are accrued. Iraqi guideline based on international European Leukemia Net (ELN) 2013 guiding principle had been employed to evaluate the molecular response to TKI. Venous blood samples have been taken for detection of T315I mutation in eligible registered patients. Results A total of fifty patients eligible for the study have been included out of 72 registered patients, 24 (48%) patients have been resistant while 26 (52%) were responding to TKIs treatment. T315I mutation turned into detected in 4/24 (16.7%) of resistant patients. The proportion of patients with T315I mutation were higher than that of control group, with a significant risk association to develop resistance to TKI therapy (odd ratio 2.3, C.I.?=?1.654–3.198). Conclusion T315I mutation become determined to be significantly higher in patient resistance to TKI than the ones responding group which can also play apposition inside the etiology for resistance development against TKI therapy.