Correlation of EZH2 and related signaling molecules p-STAT3, p-ERK1/2, and MYC overexpression with H3K27 trimethylation associates differently to disease progression in JAK2 mutation -positive and -negative myeloid neoplasms

EZH2 is an important epigenetic regulator in malignant neoplasms. We investigated the tumorigenic roles of EZH2 and intracellular molecules in <i>JAK2+/-</i> myeloid neoplasms. EZH2 is upregulated in AML and non-leukemic myeloid neoplasms (M/N) and is associated with H3K27me3 co-expression. EZH2 overexpression is correlated with p-STAT3 and MYC upregulation in <i>JAK2+</i> M/N, but only with MYC activation in <i>JAK2-</i> M/N. In <i>JAK2+</i> myeloid neoplasms, p-STAT3, p-ERK1/2, and MYC showed a significantly elevated percentage of tumor cell positivity in AML compared to M/N group. In <i>JAK2-</i> cases, MYC, but not p-STAT3 or p-ERK1/2, showed significantly elevated percentage of tumor cell positivity in AML compared to M/N group. In conclusion, EZH2 plays an oncogenic role through overexpression in its wild-type myeloid neoplasms. EZH2, p-STAT3, MYC, and p-ERK1/2 upregulation associate differently with disease progression depending on <i>JAK2</i> mutation status. EZH2 and related signaling molecules could serve as potential therapeutic targets in myeloid neoplasms.