SF3B1 mutant-induced missplicing of MAP3K7 causes anemia in myelodysplastic syndromes

Significance Myelodysplastic syndromes (MDS) are the most commonly diagnosed malignancy of the elderly in the United States, but what causes severe anemia in MDS has been unknown. Our findings provide a detailed mechanism underlying the origins of severe anemia and other cardinal phenotypes in MDS patients harboring SF3B1 mutations, which are found in about a quarter of all MDS patients. In addition, we define a role of MAP3K7 and a MAP3K7-p38 MAPK axis in human terminal erythroid differentiation and created a SF3B1 cell model that recapitulates many of the terminal erythroid differentiation events of mutant SF3B1 MDS patients, which should prove valuable for developing novel drugs and therapies.