Frequency of BCR-ABL1 transcripts in chronic Myeloid Leukemia
Date
2021
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Department of Biotechnology
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.
Description
Keywords
BCR-ABL1, Chronic Myeloid Leukemia, Nepalese population, Real-time PCR