Blood: CalR single-dose insufficient to enhance the activity of hematopoietic stem cells, participation in MPN occurrence

The JAK2, MPL or CALR gene mutations are found in patients with more than 80% of myeloid hyperplasia tumors (MPNs) and are thought to play a driving role in THE MPN pathogenesis through autosomal activation of the JAK-STAT signal cascade reactionIn mice, the mutant CALR binds to MPL to activate the downstream MPL signal cascade reaction and induce primary platelet growthbut the embryonic lethality of Calr defective mice prevented us from studying the role of CALR in hematopoietics through the mouse modelIn order to clarify the role of CALR in normal hematopoietic and MPN pathology, Shide et alestablished hematopoietic-specific Calr defective miceThere was no significant effect on white blood count, hemoglobin level, or platelet count in circumsal bloodHowever, Calr defective mice exhibited certain hematopoietic properties of MPN, including reduced red blood cell production and an increase in myelin progenitor cells in the bone marrow, as well as exoblastation in the spleentransplant experiments showed that calr single-dose insufficient dose will promote the self-renewal of hematopoietic stem cellsThe researchers also established a model of calRdel52 mutant mice with Calrdel52 mutations as a model for simulated human MPN patients, and found that Calr's single dose was insufficient to restore the self-renewal of hematopoietic stem cells destroyed by the CALR mutationonly mice that were transplanted with both CALR mutations and Carr single-dose insufficient Lineage-Sca1 plus c-kit-plus cells were able to develop MPN under competitive conditions, indicating that the incidence of CALR mutant MPNs required the participation of CALR single dose