Therapeutic Targeting of RNA Splicing in Myelodysplasia

Genomic analysis of patients with myelodysplastic syndromes (MDS) has identified that mutations within genes encoding RNA splicing factors represent the most common class of genetic alterations in MDS. These mutations primarily affect SF3B1, SRSF2, U2AF1, and ZRSR2. Current data suggest that these mutations perturb RNA splicing catalysis in a manner distinct from loss of function but how exactly the global changes in RNA splicing imparted by these mutations result in MDS is not well delineated. At the same time, cells bearing mutations in RNA splicing factors are exquisitely dependent on the presence of the remaining wildtype allele to maintain residual normal splicing for cell survival.

Source: Seminars in Hematology - July 12, 2017 Category: Hematology Authors: Young Joon Kim, Omar Abdel-Wahab Source Type: research