Role of JAK2 V617F in Myeloproliferative Neoplasms: From Mutation to Manifestation: A Review

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by excessive production of one or more mature myeloid lineages. The JAK2 V617F point mutation - present in nearly all patients with polycythemia vera (PV) and in approximately 50% of those with essential thrombocythemia (ET) and primary myelofibrosis (PMF) - is the principal molecular driver in Philadelphia chromosome (Ph)-negative MPNs. This review, conducted in accordance with PRISMA 2020 guidelines, aimed to evaluate the clinical manifestations (thrombosis, splenomegaly, and bleeding), hematological parameters, serum lactate dehydrogenase (LDH) levels, and risk of disease progression to acute leukemia or myelofibrosis associated with the JAK2 V617F mutation. A comprehensive literature search was performed across PubMed/MEDLINE, Embase, Scopus, and Web of Science for studies published between 2005 and 2025. Following screening of 1,100 candidate records, 10 primary studies encompassing 3,311 patients were included in the final synthesis. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). The included studies demonstrate that the majority of JAK2 V617F-positive MPN patients are older than 50 years, with no marked sex predilection. Splenomegaly and thrombotic events were frequently reported across cohorts. Serum LDH levels, hematocrit, and hemoglobin were consistently elevated, while leukocytosis was the predominant hematological finding, though white blood cell (WBC) counts varied widely across MPN subtypes. A minority of patients demonstrated disease transformation to acute leukemia or myelofibrosis. These findings underscore the central prognostic and diagnostic significance of JAK2 V617F in Ph-negative MPNs and highlight its value in clinical risk stratification and therapeutic monitoring.