Prognostic Implication of BCR-ABL Fusion Transcript Variants in Chronic Myeloid Leukemia (CML) Treated with Imatinib. A First of Its Kind Study on CML Patients of Kashmir

Abstract

Background: The prognostic significance of the common BCR-ABL transcripts like e13a2 (b2a2) and e14a2<br />(b3a2) in Chronic myeloid leukemia (CML) has been reported from patients treated with different tyrosine kinase<br />inhibitors but its impact on clinical response and overall survival remains still unexplored. The aim of this study was<br />to evaluate the prognostic significance of different transcript types in a cohort of CML patients treated with imatinib.<br />Methods: A total 42 confirmed cases of Chronic Myeloid Leukemia (CML) patients were recruited into our cohort<br />study and a multiplex Reverse Transcriptase-Polymerase Chain Reaction technique (RT-PCR) was used to detect 3 main<br />transcript types ‘e1a2', ‘e13a2', and ‘e14a2' found in CML. Results: Only two types of transcripts e13a2 (b2a2) and<br />e14a2 (b3a2) were detected in our CML patients and none had the e1a2 type. All the patients were RT-PCR positive<br />for either e13a2 or e14a2 fusion transcript demonstrating 100% concordance with their Ph+ve cytogenetic status at<br />baseline. TLC count (range of 201-600x103/μl) and platelet count (range of 201-900x103/μl) at baseline were found to<br />be associated more with the e14a2 (b3a2) than the e13a2 (b2a2) transcript type (p-value: 0.001). The two transcripts<br />found did not relate significantly towards sex, age-group or indicated spleen size ranges as well as percentage ranges<br />of blast cells. Conclusion: We conclude that there is no overall prognostic implication of either the e13a2 or the e14a2<br />transcript type across the spectrum of indicated clinical parameters evaluated. Even the overall survival analysis of the<br />two transcript types revealed no prognostic association whatsoever.