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Mechanism of leukemogenesis due to loss-of-function mutation in EZH2. Loss-of-function mutations in EZH2 increase transcription of stem-cell and early-progenitor related genes including HOXA. It results into differentiation block of thymocytes. Moreover, the transcription of IL6RA is increased due to loss-of-function EZH2 mutations. Thus, the expression of IL6 receptor is increased and causes hyperresponsiveness to IL6 which results into hyperactivation of STAT3.
