A comprehensive analysis of breakpoint cluster region-abelson fusion oncogene splice variants in chronic myeloid leukemia and their correlation with disease biology.
Loading...
Date
2014-01
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
BACKGROUND: BCR-ABL fusion oncogene is a hallmark
of Chronic Myeloid Leukemia (CML). It results due to
translocation between chromosome 22 and chromosome 9
[t (9; 22)(q34; q11)]. It gives rise to translation of a 210 KDa
chimeric protein (p210), leading to enhanced tyrosine kinase
activity and activation of leukemogenic pathways, ultimately
causing onset of CML. In case of CML, the classic fusions are
b2a2 or b3a2, fusing exon 13 (b2) or exon 14 (b3) of BCR,
respectively, to exon 2 (a2) of ABL. The type of BCR-ABL
transcripts are thought to be have different prognosis and
hence useful in clinical decision-making. The frequencies of
different fusion oncogenes associated with leukemia can vary
in different ethnic groups and geographical regions due to
interplay of genetic variation in different ethnic populations,
diverse environmental factors and living style. Moreover,
earlier relevant studies from our region were carried out in
small subset of patients. Therefore, objective of this study
was to find out frequencies of different BCR-ABL splice
variants in larger subset of CML patients.
METHODS: A nested reverse transcriptase polymerase
chain reaction (RT-PCR) was established to detect BCRABL
splice variants in 130 CML patients. Sensitivity of
RT-PCR and ability to detect BCR-ABL fusion gene in least
possible time was studied.
RESULTS: BCR-ABL detection using our optimized RTPCR
protocol could be completed in 8 hours, starting from
RNA extraction to Gel electrophoresis. Sensitivity of RTPCR
assay was of the order of 10−6. Out of 130 Pakistani patients, 83 (63.84%) expressed b3a2 while 47 (36.15%)
expressed b2a2 transcript.
CONCLUSION: Our RT-PCR was proved to be very quick
to detect BCR-ABL fusion oncogene in CML patients within
one working day. Because of its sensitivity, it can be used
to monitor complete molecular response in CML. BCR-ABL
RT-PCR and BCR-ABL splice variants frequency in our
study differs from other ethnic groups. It shows that ethnic
and geographical differences exist in BCR-ABL splice
variant frequency, which may have a profound effect on
disease biology as well as implications in prognosis and
clinical management of BCR-ABL positive leukemias.
Description
Keywords
b2a2, b3a2, breakpoint cluster region‑abelson, breakpoint cluster region‑abelson alternative splicing
Citation
Iqbal Zafar. A comprehensive analysis of breakpoint cluster region-abelson fusion oncogene splice variants in chronic myeloid leukemia and their correlation with disease biology. Indian Journal of Human Genetics. 2014 Jan-Mar ;20 (1): 64-68.