Cancers, Vol. 11, Pages 1844: Mutations in Splicing Factor Genes in Myeloid Malignancies: Significance and Impact on Clinical Features

Cancers, Vol. 11, Pages 1844: Mutations in Splicing Factor Genes in Myeloid Malignancies: Significance and Impact on Clinical Features Cancers doi: 10.3390/cancers11121844 Authors: Valeria Visconte Megan O. Nakashima Heesun J. Rogers Components of the pre-messenger RNA splicing machinery are frequently mutated in myeloid malignancies. Mutations in LUC7L2, PRPF8, SF3B1, SRSF2, U2AF1, and ZRSR2 genes occur at various frequencies ranging between 40% and 85% in different subtypes of myelodysplastic syndrome (MDS) and 5% and 10% of acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs). In some instances, splicing factor (SF) mutations have provided diagnostic utility and information on clinical outcomes as exemplified by SF3B1 mutations associated with increased ring sideroblasts (RS) in MDS-RS or MDS/MPN-RS with thrombocytosis. SF3B1 mutations are associated with better survival outcomes, while SRSF2 mutations are associated with a shorter survival time and increased AML progression, and U2AF1 mutations with a lower remission rate and shorter survival time. Beside the presence of mutations, transcriptomics technologies have shown that one third of genes in AML patients are differentially expressed, leading to altered transcript stability, interruption of protein function, and improper translation compared to those of healthy individuals. The detection of SF mutations demonstrates the importance of splicing abnormalities in the hematopoiesis of MDS and A...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research