Physiological MplW514L expression in hematopoietic stem cell causes an essential thrombocythemia and progressive myelofibrosis
Shujing Zhang·Baobing Zhao·Yuan Li·Yi Wang·Lingling Wang·Miaomiao Xu·Yanxia Li·Ge Dong·Shanshan Wang·Yanmei Li·Zhigang Cai·Jingjing Liu
Typ515 (W515) mutations in the protein MPL are one of key driver mutations promoting BCR/ABL-negative myeloproliferative neoplasms (MPNs), but their effects on hematopoietic stem cells (HSCs) and MPN-related hematological abnormalities have not been studied in physiological contexts. Here, we established a MplW514L knock-in mouse model which largely mimics human MPLW515L mutation during hematopoiesis. The mutant mice developed an essential thrombocythemia (ET)-like MPN phenotypes, displaying exc