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

著者: Yen K. Lieu, Zhaoqi Liu, Abdullah Mahmood Ali, Xin Wei, Alex Penson, Jian Zhang, Xiuli An, Raúl Rabadán, Azra Raza, James L. Manley, Siddhartha Mukherjee - Proceedings of the National Academy of Sciences, PNAS 2021 被引用: 58

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.