MPNs

MPNs, or myeloproliferative neoplasms, are Philadelphia chromosome–negative hematologic cancers characterized by clonal proliferation of myeloid cells driven by acquired mutations that activate the JAK-STAT signaling pathway. They largely affect adults and may present with high red cell mass, high platelet counts, splenomegaly, or symptoms such as fatigue and pruritus.

The classical MPNs are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). They share a risk of progression to myelofibrosis or acute leukemia and a tendency toward thrombotic or bleeding complications.

Driver mutations include JAK2 V617F, CALR, and MPL. JAK2 V617F is present in most PV and in many ET and PMF cases; CALR or MPL mutations occur mainly in ET and PMF. These mutations aid diagnosis with clinical and morphologic data.

Clinical features include elevated counts, splenomegaly, pruritus (PV), erythromelalgia, and anemia or leukoerythroblastosis in PMF. Complications include thrombosis, bleeding, and progression to marrow fibrosis or leukemia.

Diagnosis uses blood counts, marrow examination, and mutation testing, integrated with WHO criteria and risk assessment. Management aims to lower thrombotic risk, control blood counts, and treat symptoms; regular monitoring is essential.

Treatments are risk-adapted. PV: phlebotomy to maintain hematocrit and low-dose aspirin; high-risk patients may receive cytoreduction with hydroxyurea or interferon. ET: low-dose aspirin and cytoreduction for high-risk disease. PMF: JAK inhibitors for symptoms and splenomegaly, with stem cell transplantation in selected cases.