promotes clonal hematopoiesis in mice with loss of function.

Hematopoietic malignancies emerge through the acquisition of genetic mutations within hematopoietic stem and progenitor cells (HSPCs). Some mutations impart a selective growth advantage to HSPCs, which expand and contribute to mature blood cells. This expansion is termed clonal hematopoiesis (CH). Inhibitor of DNA binding 1 (ID1) protein is a transcriptional regulator of proliferation/differentiation of hematopoietic cells. HSPCs express low levels of that is induced by growth factors and other mediators of inflammatory during stress to promote HSPC expansion. Since chronic inflammation is associated with the progression of hematopoietic malignancies, reducing expression may reduce CH. Genetic ablation of in HSPCs reduces HSPC expansion/CH, extramedullary hematopoiesis, myeloid skewing, and genetic instability and delays the onset of disease. Mechanistically, p16 expression, senescence, and apoptosis were increased, and proliferation decreased in HSPCs. Thus, ID1 may represent a therapeutic target to reduce CH and delay the onset of disease.