[Deregulated RNA processing in leukemias]

Abstract

RNA processing, including splicing, polyadenylation, and capping, plays a central role in post-transcriptional gene regulation. Recent genomic studies have revealed frequent mutations in RNA processing factors, particularly splicing factors such as SF3B1, SRSF2, U2AF1, and ZRSR2, in hematologic malignancies. These mutations result in aberrant splicing, contributing to tumorigenesis and disease progression. In this review, we summarize the molecular consequences of these mutations and their pathophysiological impact. We discuss shared downstream mechanisms such as R-loop accumulation, impaired transcriptional elongation, and the generation of immunogenic neoantigens derived from abnormal splicing. We also review recent advances in therapeutic strategies targeting splicing dysregulation, including small molecule splicing modulators and antisense oligonucleotides. These approaches offer the potential for selective targeting of cancer cells with aberrant RNA processing. Novel strategies to exploit splicing abnormalities for cancer treatment are emerging as understanding of RNA processing biology progresses and precision RNA-based therapeutics are developed.

Keywords: Leukemia; RNA processing; Splicing; Splicing modulator.