We envision a model whereby RUNX1 mutations increase the rate at which secondary mutations are acquired; moreover, increased inflammatory signals delivered by RUNX1 mutant myeloid lineage cells or other cells in the RUNX1 mutant bone marrow microenvironment provide a selective pressure that confers a competitive advantage to FPD/AML HSCs that have acquired secondary mutations (Figure 1). Here, RUNX1 is linked to acute myeloid leukemia.