Murine analyses conducted by Muto et al. revealed that EZH2 or TET2 deficiency alone is sufficient to induce an MDS/MPN phenotype with lethality during long observation periods, while depletion of both EZH2 and TET2 synergistically advances myelodysplasia and accelerates the progression of both MDS and MDS/MPN. The gene discussed is EZH2; the disease is myelodysplastic syndrome.