Myeloproliferative neoplasms (MPN) are marked by the overproduction of myeloid cells, driven by JAK2, CALR, and MPL mutations. A recent study aimed to explain how these mutations result in various MPN phenotypes by sequencing 1,711 genes and performing whole transcriptome RNA sequencing in 137 patients with MPN. Findings, which were published online in Clinical Cancer Research, revealed 234 mutated genes in overt myelofibrosis (MF) and 74 in essential thrombocythemia (ET), polycythemia vera (PV), and prefibrotic primary myelofibrosis (prePMF), with MF showing more mutations per patient. High-risk and Ras pathway genes were frequently mutated in MF, correlating with advancing age, higher DIPSS scores, and poorer overall survival (OS). Ras mutations were linked to increased leukocytes and platelets and worse OS. Gene expression analysis indicated upregulation of proliferative and inflammatory pathways in MF. These results suggest MF evolution from ET/PV/PrePMF is driven by age-related mutation accumulation and proliferative pathway activation, offering potential targets for therapeutic intervention.