Splicing dysregulation in human hematologic malignancies: beyond splicing mutations

Abstract

Splicing is a fundamental process in pre-mRNA maturation. Whereas alternative splicing (AS) enriches the diversity of the proteome, its aberrant regulation can drive oncogenesis. So far, most attention has been given to spliceosome mutations (SMs) in the context of splicing dysregulation in hematologic diseases. However, in recent years, post-translational modifications (PTMs) and transcriptional alterations of splicing factors (SFs), just as epigenetic signatures, have all been shown to contribute to global splicing dysregulation as well. In addition, the contribution of aberrant splicing to the neoantigen repertoire of cancers has been recognized. With the pressing need for novel therapeutics to combat blood cancers, this article provides an overview of emerging mechanisms that contribute to aberrant splicing, as well as their clinical potential.

Keywords: emerging treatments; hematologic cancers; post-translational regulation; splicing; therapeutics.