Contrasting Stage Dependent Requirements For The Histone Methyltransferase Ezh2 During The Evolution Of Acute Myeloid Leukemia

Epigenetic regulators function in a context-dependent manner and are commonly mutated in tumors. Activating mutations and overexpression of the histone-methyltransferase, enhancer of zeste, homolog 2 (EZH2), occur in lymphoma and other malignancies, whilst loss-of-function mutations are predicted in myeloid malignancies. We study this apparent contradiction, examining the importance of cellular context and disease stage for Ezh2 loss, genetically deleting Ezh2 during the induction or maintenance of a single malignancy, Acute Myeloid Leukemia (AML).