High levels of RUNX1 are required to induce myeloid differentiation genes such as Cebpa, Sfpi1 and Irf8. This suggests that the crucial differences in the transcriptional networks of HE and progenitor cells are caused by differential levels of RUNX1 and that RUNX1-ETO could directly interfere with RUNX1 binding to its targets. The gene discussed is SPI1; the disease is hereditary elliptocytosis.