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

Document Type: Research Articles

Authors

1 Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.

2 Advanced Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.

3 Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.

4 Department of Clinical Hematology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.

5 Department of Medical Oncology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

Abstract

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

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