To identify the oncogenic transcriptional pathways repressed by Ezh2 and the mechanisms that facilitate accelerated transformation following its loss, we performed differential global gene expression analysis using RNA-seq in Ezh2+/+ and Ezh2−/− nontransformed (“premalignant”) Lin− HSPCs (Fig. 5 a), comparing this to similar datasets generated in Ezh2+/+ and Ezh2−/− AML1-ETO9a and MLL-AF9 leukemias (Fig. 5, b and c). The gene discussed is KMT2A; the disease is leukemia.