Figure 7: Predicted model for sequential acquisition of genetic lesions in MDS to AML transformation.
From: SF3B1 mutant MDS-initiating cells may arise from the haematopoietic stem cell compartment
SF3B1 mutations are acquired in CD34+CD38−CD90+CD45RA−CD49f+ HSCs. As HSCs replenish downstream progenitors, mutations acquired in stem cells are also propagated to mature progenitors but without conferring self-renewal potential. However, as the mature progenitors such as MLPs harbouring a mutant SF3B1 acquires a more ‘potent hit’ such as SUV420H1 mutation, they confer self-renewal potential and suppress the HSC to MPP transition.
