Ezh2 deletion has switched the MPN phenotype. (A) Jak2V617F knock-in mice develop a PV-like phenotype that progresses after 6 months into MF. Ezh2 deletion has switched Jak2V617F knock-in mice to an ET phenotype, quickly progressing to MF. (B) Ezh2 deletion in cooperation with Jak2V617F led to an increase in TNF-α, JNK, and IFN-α signaling, and overexpression of derepressed target genes such as S100a8, S100a9, Ifi27l2a, or Hmga2. Over-expression of these genes in Jak2V617F cells induces an MF phenotype.