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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Myeloproliferative neoplasms are slow-growing blood cancers in which the marrow overproduces red cells (polycythaemia vera), platelets (essential thrombocythaemia) or scar tissue (myelofibrosis). Almost all carry a mutation in JAK2, CALR or MPL; treatment aims to prevent clots and control symptoms, and only transplant cures myelofibrosis.
The classical BCR-ABL1-negative MPNs (polycythaemia vera, essential thrombocythaemia, primary myelofibrosis) are clonal diseases driven by JAK-STAT activation: JAK2 V617F in ~95% of PV and ~60% of ET/PMF, CALR in ~25% of ET/PMF, MPL in ~5%. Risk in PV/ET is thrombosis (managed with aspirin, phlebotomy, hydroxyurea or interferon); in myelofibrosis it is cytopenias, splenomegaly, constitutional symptoms and leukaemic transformation (about 10-20%), risk-scored by DIPSS-plus, MIPSS70 and MIPSS70+ v2.0.
Ruxolitinib (COMFORT-I/II, 2011) was the first JAK inhibitor; fedratinib (2019), pacritinib (2022, for platelets <50) and momelotinib (2023, for anaemic patients) followed. None is disease-modifying: allogeneic transplant remains the only cure for myelofibrosis. Ropeginterferon alfa-2b (2021) is the first approved interferon for PV with evidence of molecular response, and rusfertide (2026), a hepcidin mimetic, is the first drug to control PV erythrocytosis without phlebotomy (VERIFY). CALR-directed antibodies and JAK2 V617F-selective inhibitors are the disease-modifying hope; pelabresib (BET inhibitor) plus ruxolitinib improved spleen response but not symptoms in MANIFEST-2.
| Setting | Approach | Guideline |
|---|---|---|
| PV | Low-dose aspirin, phlebotomy to haematocrit <45%; cytoreduction (hydroxyurea or ropeginterferon alfa-2b) for high-risk; ruxolitinib after hydroxyurea failure (RESPONSE); rusfertide to eliminate phlebotomy need (VERIFY, 2026). | NCCN Category 1 (ropeginterferon, hydroxyurea) |
| ET | Risk-adapted (IPSET-thrombosis): observation or aspirin in low risk; hydroxyurea or interferon in high risk; anagrelide second line. | not mapped |
| Myelofibrosis, intermediate-2/high risk | JAK inhibitor for spleen and symptoms: ruxolitinib (COMFORT), fedratinib, pacritinib if platelets <50×10⁹/L, momelotinib if anaemic (MOMENTUM); allogeneic HSCT for eligible patients (the only cure). | NCCN Category 1 (ruxolitinib, fedratinib); 2A (pacritinib, momelotinib) |
| Anaemia of myelofibrosis | Momelotinib, luspatercept (INDEPENDENCE), ESA, danazol, transfusion. | not mapped |