Cancer-Associated Mutations in SF3B1 Exhibit Neomorphic Splicing Activity and Block Erythroid Differentiation

Recently, heterozygous mutations in several spliceosome genes have been observed in hematological and solid cancers, but their functional role in these diseases is not well understood. Among these, SF3B1 is the most commonly mutated spliceosome gene in myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL). SF3B1 is part of the U2 complex involved in the recognition of the 3’ splice sites (3’ss) during early spliceosome assembly.