Therefore, our single cell profiling, flow cytometry, and histopathology uncovered a functional cooperation between NRasG12D activation and EZH2-deficiency to induce MEP expansion and skewed lineage differentiation towards megakaryocytes, leading to the development of advanced myelofibrosis in G12D/E2-KO mice. This evidence concerns the gene EZH2 and myelofibrosis.