SF3B1 Mutations in Hematological Malignancies

Abstract

Recently, mutations in the genes involved in the spliceosome have attracted considerable interest in different neoplasms. Among these, SF3B1 mutations have acquired great interest, especially in myelodysplastic syndromes, as they identify a subgroup of patients who can benefit from personalized therapy. The SF3B1 gene encodes the largest subunit of the splicing factor 3b protein complex and is critical for spliceosome assembly and mRNA splicing. The mutated SF3B1 gene encodes for a protein with a different mRNA processing mechanism that results in the aberrant splicing of many mRNAs, which can be downregulated. Although there are many mRNAs affected by a splicing alteration, only a few of these have been directly related to the pathogenesis of several diseases. In this review, we took a snapshot of the current knowledge on the implications of SF3B1 mutations in different hematological malignancies.

Keywords: SF3B1; hematological malignancies; patient stratification; spliceosome mutations; splicing factor.

Figure 1

Schematic representation of the most frequent mutations of the SF3B1 gene that characterize hematological neoplasms. The numbers 5, 6, 7 an 8 in the figure correspond to the non-identical HEAT repeats most frequently affected by mutations. (the figure was modified from Servier Medical Art, licensed under a Creative Common Attribution 3.0 Generic License, http://smart.servier.com/, accessed on 17 August 2022).

Figure 2

Schematic representation of SF3B1 wild-type (wt)-mediated splicing, which generates canonical transcription and translation, and SF3B1-mutated (mut)-mediated splicing, which results in aberrant/alternative transcription. As a consequence, premature stop codons (PTC) can form, leading to the down-expression of canonical proteins or the translation of new proteins with aberrant functions (the figure was modified from Servier Medical Art, licensed under a Creative Common Attribution 3.0 Generic License, http://smart.servier.com/, accessed on 18 August 2022).