A small sample size study found that an initiating event in the pathogenesis of SF3B1 mutant MDS- RS originates in a rare population of HSCs and propagates the mutation to their myeloid hematopoietic progenitor cells (HPCs) and de novo mutations acquired by HPCs at later stages of the disease can confer self-renewal capacity to MDS to drive the transition to leukemia (39). The gene discussed is SF3B1; the disease is myelodysplastic syndrome.