The Prevalence of G250E and Y253F among ABL Kinase Domain Mutations and its Relation with Resistance to Tyrosine Kinase Inhibitors in Patients with CML in Middle Euphrates of Iraq

Abstract

Background: Chronic Myeloid Leukemia (CML) is a hematopoietic stem cell disease, associated with a reciprocal translocation between chromosomes 9 and chromosome 22, lead to the formation of the BCR-ABL fusion gene (Philadelphia chromosome). This fusion gene is believed to play a golden role in the initial development of CML with constitutive tyrosine kinase activation. Successful use of tyrosine kinase inhibitors (TKIs) plays a role in improve survival and increases the prevalence of CML, but unfortunately mutations in the BCR-ABL kinase domain may cause, or contribute to increasing, resistance to TKIs in CML patients.
Objective: This study was designed to assess the association of two common BCR-ABL kinase domain mutations (G250E and Y253F) with resistance state of CML patients on TKIs in the Iraqi Middle Euphrates region.
Patients and Methods: A retrospective case-control study in which 85 patients with chronic myeloid leukemia in chronic phase (45 patients as cases group and 40 patient as a control group) were selected from three hematooncology centers in the middle Euphrates in Iraq during the period from January 2016 till October 2016 out of a total of 240 CML patients (108 male and 132 female) who were registered during this period in these three centers and all patients on TKI (Imatinib and Nilotinib).
Results: One patient from the cases group (1/45) was carriers of one of two selected ABL kinase domain mutations and no one of the control groups. G250E was detected in 1/45 (2.2 %) and also had significant risk association to develop resistance to TKIs odd ratio, C.I., 2.73, 0.1081-68.9424. This mutation had no significant correlation with demographic or hematological features.Y253F was not detected in any one of our study groups CML patients.
Conclusions: G250E among selected ABL kinase domain mutations were detected in our CML patients with resistance to TKIs. This mutation may play a role in the development variable degree of resistance to first and second-generation TKIs whether primary or secondary.