Frequency of BCR-ABL1 transcripts in chronic Myeloid Leukemia

Abstract

FREQUENCY OF BCR-ABL1 TRANSCRIPTS IN CHRONIC MYELOID LEUKEMIA. Background: Chronic myeloid Leukemia (CML) is among the largest group of leukemia cases in Nepal. Underlying pathology in CML is the translocation between ABL1 gene and BCR gene. The breakpoint in the BCR and ABL1 gene may vary leading to the formation of various types of fusion transcripts viz. p210, p190, p230 and other rare variants. Literatures suggest p210 is the most common transcript type seen in CML. Eventhough rare, the variants such as p190 and p230 have also been reported. However, studies are lacking to see the transcript type of CML patients in Nepal. Molecular diagnosis of CML is mostly done in the referral laboratories in India. In this study, we tried to analyse the frequency of different BCR-ABL1 transcripts (p210, p190, p230) in Nepalese CML patients in a laboratory within Nepal. In addition, the response of different transcripts towards drugs being used was also analysed via protein-ligamd interaction. A total of 45 samples were studied using real-time and conventional method and virtual screening approaches were explored to study drug interactions. Methodology: During the study period, a total of 45 cases of suspected CML patients were included. Total RNA was extracted and reverse transcribed to cDNA using standard protocols. qPCR was performed with primers and probes targeting p210, p190 and p230 transcripts. The protein-ligand study was carried out using docking tools. All the results were statistically analysed. Results: Almost all the cases, 44/45 cases (97.7%) were positive for p210 transcript only. CML was found to be more common in males with M:F ratio of 2.44 : 1. The disease was more prevalent in Kshetri community. The disease was more common in middle aged population with median age of 43 years at diagnosis. Transcript type variation made no impact to drug affinity in CML patients. Conclusion: p210 transcript is the most prevalent transcript type in our study. Hence p210 must be targeted in the suspected cases of CML. Transcript type made no effect in drug use however larger studies may be informative regarding the frequency of other rare variants in Nepalese patients and developing effective treatments.

Keywords: BCR-ABL1, Chronic Myeloid Leukemia, Nepalese population, Real-time PCR, Transcripts, Docking.