Role for RNA-Binding Protein in Progression of CML
Posted: Thursday, April 25, 2019
Aberrant polypyrimidine tract binding protein 2 (PTB2) may play an important role in the progression of chronic myeloid leukemia (CML). PTB2, an RNA-binding protein, contributes to the regulation of alternative splicing in neurons; recently, its presence has indicated “oncogenic potential” for some cancer types. According to Soumen Chakraborty, PhD, of the Institute of Life Sciences in Bhubaneswar, India, and colleagues, increased levels of functional PTB2 protein correlated closely with progression of CML. Their study results were published in the International Journal of Biochemistry and Cell Biology.
“Our study portrays PTBP2 as a new possible target for CML, and progressive inclusion/exclusion of [PTBP2] exon 10 might play an important role in CML progression,” concluded the authors.
In this study, the authors analyzed the gene-expression profiles of 26 patients with CML in the blast phase. They found that PTB2 mRNA levels were positively correlated to blast count (P = .0195), and their relative levels were higher than that of most (8 out of 9) of the other RNA-binding proteins evaluated. In patients with relapsed disease, relative PTB2 mRNA levels were even higher, and paired analysis of these patients showed higher PTB2 mRNA levels in the blast phase than in the chronic phase.
Furthermore, the authors found increased PTB2 exon 10 expression in 32Dcl3 BCR-ABL1 cells (P = .0073), as well as 3 CML cell lines (KCL22, K562, and KYO-1), and that this was dependent on the BCR-ABL1 kinase domain. Functional PTB2 protein was detected as a result of exon 10 expression. Lastly, the authors knocked down PTB2 using shRNA in KCL22 cells and found reduced cell proliferation, increased cell-cycle arrest, and apoptosis.
Disclosure: The study authors reported no conflicts of interest.