Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: June 9, 2022

Abstract Background The dynamic epigenome and proteins specialized in the interpretation of epigenetic marks critically contribute to leukemic pathogenesis but also offer alternative therapeutic avenues. Targeting newly discovered chromatin readers involved leukemogenesis may thus provide new anticancer strategies. Accumulating evidence suggests that PRC1 complex member CBX2 is overexpressed solid tumors promotes cancer cell survival. However, its role leukemia still unclear. Methods We exploited reverse genetic approaches investigate human lines ex vivo samples. analyzed phenotypic effects following silencing using cellular molecular assays related functional mechanisms by ATAC-seq RNA-seq. then performed bioinformatic analysis ChIP-seq data explore influence histone modifications CBX2-mediated open sites. Lastly, we used determine contribution CBX2-regulated pathways phenotype. Results found both vitro samples compared CD34 + cells. Decreased RNA levels prompted a robust reduction proliferation induction apoptosis. Similarly, sensitivity was observed primary acute myeloid suppression increased genome-wide accessibility followed alteration transcriptional programs, resulting enrichment death downregulation survival genes. Intriguingly, induced reprogramming at p38 MAPK-associated regulatory sites with consequent deregulation gene expression. Conclusions Our results identify as crucial player progression highlight potential druggable CBX2-p38 MAPK network AML.

Language: Английский