A “two-hit” model was proposed for MDS progression to AML [(first-hit: mutations in genes affecting the differentiation of cells (TET2, RUNX1) followed by the second-hit in the genes that influence the proliferation and survival of cells (FLT3, NPM1, IDH1, IDH2)] [33]. The gene discussed is RUNX1; the disease is acute myeloid leukemia.