# Myeloproliferative neoplasms (PV, ET, myelofibrosis)

Source: https://onco.cc/cancers/myeloproliferative-neoplasms/  
OnCo record `myeloproliferative-neoplasms` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Also known as: MPN; Polycythaemia vera; Essential thrombocythaemia; Primary myelofibrosis
- Tags: gap-fill; haematologic
- Group: haematologic
- Burden: Combined incidence around 2-3 per 100,000 per year; PV and ET are chronic diseases lived with for decades, myelofibrosis has a median survival of about six years.
- Subtypes: Polycythaemia vera (PV); Essential thrombocythaemia (ET); Prefibrotic and overt primary myelofibrosis (PMF); Post-PV / post-ET myelofibrosis; MPN in blast phase; Triple-negative MPN
- Biomarkers: JAK2 V617F and exon 12; CALR type 1/2; MPL W515; High-molecular-risk mutations (ASXL1, EZH2, SRSF2, IDH1/2, U2AF1); DIPSS-plus / MIPSS70+ v2.0; Haematocrit target <45% (CYTO-PV); Platelet count (pacritinib eligibility)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/myeloproliferative-neoplasms/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/myeloproliferative-neoplasms/#overview [3 subtypes, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/myeloproliferative-neoplasms/#what-it-is [9 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/myeloproliferative-neoplasms/#finding-it [7 biomarkers, 2 prevalence rows]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/myeloproliferative-neoplasms/#treating-it [4 settings, 4 decisions with options]
- Evidence (own page): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/myeloproliferative-neoplasms/evidence/ [37 trials, 3 key papers, 10 milestones]
- The science (own page): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/myeloproliferative-neoplasms/science/ [93 targets, 1 pathway]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/myeloproliferative-neoplasms/where-you-are/ [1 centre]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/myeloproliferative-neoplasms/#living-with-it [18 questions, 3 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/myeloproliferative-neoplasms/coming/ [18 medicines, 37 trials, 1 idea, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/myeloproliferative-neoplasms/data/ [191 connected records]

## Standard of care

- 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). ([Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Ropeginterferon alfa-2b](https://onco.cc/drugs/ropeginterferon-alfa-2b/), [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/), [Rusfertide](https://onco.cc/drugs/rusfertide/))
- ET: Risk-adapted (IPSET-thrombosis): observation or aspirin in low risk; hydroxyurea or interferon in high risk; anagrelide second line. ([Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Ropeginterferon alfa-2b](https://onco.cc/drugs/ropeginterferon-alfa-2b/))
- 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). ([Ruxolitinib](https://onco.cc/drugs/ruxolitinib/), [Fedratinib](https://onco.cc/drugs/fedratinib/), [Pacritinib](https://onco.cc/drugs/pacritinib/), [Momelotinib](https://onco.cc/drugs/momelotinib/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [COMFORT-I](https://onco.cc/trials/comfort-i/), [COMFORT-II](https://onco.cc/trials/comfort-ii/))
- Anaemia of myelofibrosis: Momelotinib, luspatercept (INDEPENDENCE), ESA, danazol, transfusion. ([Momelotinib](https://onco.cc/drugs/momelotinib/), [Luspatercept](https://onco.cc/drugs/luspatercept/))

## State of the art

- Four approved JAK inhibitors cover spleen, symptoms, thrombocytopenia and anaemia, but none reverses fibrosis or clears the clone.
- Interferon is the only drug with consistent molecular responses in PV/ET, and ropeginterferon made it practical.
- Rusfertide (2026) is the first mechanistically new PV drug in a decade and removes the need for phlebotomy in most patients.
- The next wave targets the clone itself: mutant-CALR antibodies (e.g. INCA033989), JAK2 V617F-selective inhibitors, and navitoclax/pelabresib combinations with mixed phase 3 results.

## Open problems

- No disease-modifying therapy in myelofibrosis short of transplant.
- MPN in blast phase: outcomes as poor as secondary AML.
- Whether interferon-induced molecular response prevents progression.
- Sequencing and combining JAK inhibitors with BET, BCL-XL or CALR-directed agents.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Myeloproliferative_neoplasm
- NCCN Guidelines: MPN: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1477
- NCI PDQ: chronic MPN: https://www.cancer.gov/types/myeloproliferative/patient/chronic-treatment-pdq
- MPN Research Foundation: https://www.mpnresearchfoundation.org/

## Connected records

- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Cytokines & engineered cytokines](https://onco.cc/technologies/cytokine-therapy/), [LSD1 inhibitors](https://onco.cc/technologies/lsd1-inhibitors/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/), [Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/)
- targets: [ACVR1 (ALK2)](https://onco.cc/targets/acvr1/), [ARHGAP26](https://onco.cc/targets/arhgap26/), [ASXL1](https://onco.cc/targets/asxl1/), [BCL-2](https://onco.cc/targets/bcl2/), [BCL6](https://onco.cc/targets/bcl6/), [BLK](https://onco.cc/targets/blk/), [CALR](https://onco.cc/targets/calr/), [CBFA2T3](https://onco.cc/targets/cbfa2t3/), [CBL](https://onco.cc/targets/cbl/), [CDA](https://onco.cc/targets/cda/), [CEBPA](https://onco.cc/targets/cebpa/), [CSF2RB](https://onco.cc/targets/csf2rb/), [CUX1](https://onco.cc/targets/cux1/), [DDX41](https://onco.cc/targets/ddx41/), [ERCC4](https://onco.cc/targets/ercc4/), [ETNK1](https://onco.cc/targets/etnk1/), [ETV6](https://onco.cc/targets/etv6/), [FANCA](https://onco.cc/targets/fanca/), [FANCC](https://onco.cc/targets/fancc/), [FANCD2](https://onco.cc/targets/fancd2/), [FANCE](https://onco.cc/targets/fance/), [FANCG](https://onco.cc/targets/fancg/), [FGFR1](https://onco.cc/targets/fgfr1/), [FGR](https://onco.cc/targets/fgr/), [FYN](https://onco.cc/targets/fyn/), [GAB2](https://onco.cc/targets/gab2/), [GATA1](https://onco.cc/targets/gata1/), [GATA2](https://onco.cc/targets/gata2/), [GRB2](https://onco.cc/targets/grb2/), [IFNAR2](https://onco.cc/targets/ifnar2/), [IMPDH1](https://onco.cc/targets/impdh1/), [IRAK1](https://onco.cc/targets/irak1/), [JAK1](https://onco.cc/targets/jak1/), [JAK2](https://onco.cc/targets/jak2/), [JAK3](https://onco.cc/targets/jak3/), [LCK](https://onco.cc/targets/lck/), [MBD4](https://onco.cc/targets/mbd4/), [MDM2](https://onco.cc/targets/mdm2/), [MPL (thrombopoietin receptor)](https://onco.cc/targets/mpl/), [NSD1](https://onco.cc/targets/nsd1/), [NUP214](https://onco.cc/targets/nup214/), [PDE3A](https://onco.cc/targets/pde3a/), [PDE3B](https://onco.cc/targets/pde3b/), [PHF6](https://onco.cc/targets/phf6/), [PML](https://onco.cc/targets/pml/), [POLA2](https://onco.cc/targets/pola2/), [POLD1](https://onco.cc/targets/pold1/), [POLD2](https://onco.cc/targets/pold2/), [POLD3](https://onco.cc/targets/pold3/), [POLD4](https://onco.cc/targets/pold4/), [POLE](https://onco.cc/targets/pole/), [POLE2](https://onco.cc/targets/pole2/), [POLE3](https://onco.cc/targets/pole3/), [PPM1D](https://onco.cc/targets/ppm1d/), [PRIM1](https://onco.cc/targets/prim1/), [PRIM2](https://onco.cc/targets/prim2/), [PRKCB](https://onco.cc/targets/prkcb/), [PRKCD](https://onco.cc/targets/prkcd/), [PRKCE](https://onco.cc/targets/prkce/), [PRKCG](https://onco.cc/targets/prkcg/), [PRKCH](https://onco.cc/targets/prkch/), [PRKCI](https://onco.cc/targets/prkci/), [PRKCQ](https://onco.cc/targets/prkcq/), [PRKCZ](https://onco.cc/targets/prkcz/), [PRKD1](https://onco.cc/targets/prkd1/), [PRKD3](https://onco.cc/targets/prkd3/), [RAD21](https://onco.cc/targets/rad21/), [RARB](https://onco.cc/targets/rarb/), [RARG](https://onco.cc/targets/rarg/), [RPL5](https://onco.cc/targets/rpl5/), [RPS29](https://onco.cc/targets/rps29/), [RRM2](https://onco.cc/targets/rrm2/), [RRM2B](https://onco.cc/targets/rrm2b/), [RTEL1](https://onco.cc/targets/rtel1/), [RUNX1](https://onco.cc/targets/runx1/), [RUNX1T1](https://onco.cc/targets/runx1t1/), [SBDS](https://onco.cc/targets/sbds/), [SETBP1](https://onco.cc/targets/setbp1/), [SF3B1](https://onco.cc/targets/sf3b1/), [SH2B3](https://onco.cc/targets/sh2b3/), [SLX4](https://onco.cc/targets/slx4/), [SRMS](https://onco.cc/targets/srms/), [SRSF2](https://onco.cc/targets/srsf2/), [STAG2](https://onco.cc/targets/stag2/), [TERT](https://onco.cc/targets/tert/), [TYK2](https://onco.cc/targets/tyk2/), [U2AF1](https://onco.cc/targets/u2af1/), [WT1](https://onco.cc/targets/wt1/), [YES1](https://onco.cc/targets/yes1/), [ZRSR2](https://onco.cc/targets/zrsr2/)
- drugs: [Anagrelide](https://onco.cc/drugs/anagrelide/), [Bomedemstat](https://onco.cc/drugs/bomedemstat/), [Fedratinib](https://onco.cc/drugs/fedratinib/), [Flonoltinib](https://onco.cc/drugs/flonoltinib/), [Givinostat](https://onco.cc/drugs/givinostat/), [Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Imetelstat](https://onco.cc/drugs/imetelstat/), [JBI-802](https://onco.cc/drugs/jbi-802/), [KRT-232](https://onco.cc/drugs/krt-232/), [Luspatercept](https://onco.cc/drugs/luspatercept/), [Mitobronitol](https://onco.cc/drugs/mitobronitol/), [Momelotinib](https://onco.cc/drugs/momelotinib/), [Navitoclax](https://onco.cc/drugs/navitoclax/), [Pacritinib](https://onco.cc/drugs/pacritinib/), [Pipobroman](https://onco.cc/drugs/pipobroman/), [Ropeginterferon alfa-2b](https://onco.cc/drugs/ropeginterferon-alfa-2b/), [Rusfertide](https://onco.cc/drugs/rusfertide/), [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/)
- companies: [Bristol Myers Squibb](https://onco.cc/companies/bms/), [Disc Medicine](https://onco.cc/companies/disc-medicine/), [Geron Corporation](https://onco.cc/companies/geron/), [GSK](https://onco.cc/companies/gsk/), [Incyte](https://onco.cc/companies/incyte/), [Italfarmaco](https://onco.cc/companies/italfarmaco/), [Kartos Therapeutics](https://onco.cc/companies/kartos-therapeutics/), [Novartis](https://onco.cc/companies/novartis/), [Ryvu Therapeutics](https://onco.cc/companies/ryvu-therapeutics/)
- pathways: [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/)
- terms: [Aquagenic pruritus](https://onco.cc/terms/aquagenic-pruritus/), [ELN 2022 risk classification](https://onco.cc/terms/eln-risk/), [Erythromelalgia](https://onco.cc/terms/erythromelalgia/), [JAK2 V617F](https://onco.cc/terms/jak2-v617f/), [Post-PV myelofibrosis (spent phase)](https://onco.cc/terms/post-pv-myelofibrosis/)
- trials: [A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV)](https://onco.cc/trials/nct06985147/), [A Single-arm, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of P1101 in Adults With ET](https://onco.cc/trials/nct05482971/), [A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment](https://onco.cc/trials/nct04576156/), [A Study of LY2784544 in Participants With Myeloproliferative Neoplasms](https://onco.cc/trials/nct01594723/), [A Study of Rusfertide in Japanese Adults With Polycythemia Vera](https://onco.cc/trials/nct07648030/), [A Study to Access Efficacy and Safety of P1101 in Chinese PV Patients Who Are Intolerant or Resistance to HU](https://onco.cc/trials/nct05485948/), [A Study to Assess Efficacy, Safety, and Tolerability of P1101 in Adult Patients With PV](https://onco.cc/trials/nct05481151/), [A Study to Assess the Safety and Tolerability of BMS-986158 Alone and in Combination With Either Ruxolitinib or Fedratinib in Participants With Blood Cancer (Myelofibrosis)](https://onco.cc/trials/nct04817007/), [A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials](https://onco.cc/trials/nct04064060/), [A Study to Evaluate Safety and Efficacy of Bomedemstat (MK-3543-017)](https://onco.cc/trials/nct06351631/), [An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomi](https://onco.cc/trials/nct04717414/), [COMFORT-I](https://onco.cc/trials/comfort-i/), [COMFORT-II](https://onco.cc/trials/comfort-ii/), [CYTO-PV](https://onco.cc/trials/cyto-pv/), [Extended Access of Momelotinib in Adults With Myelofibrosis](https://onco.cc/trials/nct03441113/), [Extension Study of P1101 After Completion of Phase 2 Study in PV Patients or Phase 3 Study in ET Patients](https://onco.cc/trials/nct04655092/), [IMpactMF](https://onco.cc/trials/impactmf/), [INTREPID: A Study of Sapablursen Evaluating the Safety and Efficacy in Participants With Polycythemia Vera (PV)](https://onco.cc/trials/nct07429266/), [KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera](https://onco.cc/trials/nct03669965/), [Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms](https://onco.cc/trials/nct01761968/), [MANIFEST-2](https://onco.cc/trials/manifest-2/), [MOMENTUM](https://onco.cc/trials/momentum/), [P1101 in Treating Patients With Early PMF or Overt PMF at Low or Intermediate-1 Risk](https://onco.cc/trials/nct06468033/), [Phase 1/ Phase 2 Study to Assess Safety and Efficacy of Orally Administered JBI-802 in Subjects With Myeloproliferative Neoplasms (MPN) and Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) With Thrombocytosis](https://onco.cc/trials/nct07612280/), [Phase IIa Study of Flonoltinib Maleate Tablets in the Treatment of Patients With Polycythemia Vera](https://onco.cc/trials/nct07232290/), [PROUD-PV and CONTINUATION-PV](https://onco.cc/trials/proud-pv/), [PT-1 (Primary Thrombocythaemia 1)](https://onco.cc/trials/pt-1/), [RESPONSE](https://onco.cc/trials/response/), [Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance](https://onco.cc/trials/nct04285086/), [Study of DISC-0974 (RALLY-MF) in Participants With Myelofibrosis or Myelodysplastic Syndrome and Anemia](https://onco.cc/trials/nct05320198/), [Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN](https://onco.cc/trials/nct03386513/), [Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet Versus Best Available Therapy to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis](https://onco.cc/trials/nct04468984/), [Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis](https://onco.cc/trials/nct04562389/), [Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera](https://onco.cc/trials/nct06093672/), [Study to Assess SLN124 in Patients With Polycythemia Vera](https://onco.cc/trials/nct05499013/), [Study to Evaluate the Long-term Safety of Rusfertide (PTG-300) in Subjects With Polycythemia Vera](https://onco.cc/trials/nct06033586/), [VERIFY](https://onco.cc/trials/verify/)
- people: [Claire Harrison](https://onco.cc/people/claire-harrison/), [Joaquín Martínez-López](https://onco.cc/people/joaquin-martinez-lopez/), [Raajit K. Rampal](https://onco.cc/people/raajit-rampal/), [Srdan Verstovsek](https://onco.cc/people/srdan-verstovsek/)
- collections: [Leukemia & Lymphoma Society (LLS)](https://onco.cc/collections/leukemia-lymphoma-society/)
- key papers: [COMFORT-I: ruxolitinib, the first JAK inhibitor, versus placebo for myelofibrosis](https://onco.cc/key-papers/paper-comfort-1-ruxolitinib-myelofibrosis-nejm-2012/), [COMFORT-II: JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis](https://onco.cc/key-papers/paper-comfort-ii-ruxolitinib-best-available-therapy-harrison-nejm-2012/), [MOMENTUM: momelotinib versus danazol for myelofibrosis patients with anaemia after a prior JAK inhibitor](https://onco.cc/key-papers/paper-momentum-momelotinib-lancet-2023/)
- institutions: [Mays Cancer Center at UT Health San Antonio](https://onco.cc/institutions/mays-cancer-center/)
- cancers: [Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms](https://onco.cc/cancers/cmml/), [Essential thrombocythaemia (ET)](https://onco.cc/cancers/essential-thrombocythaemia/), [Polycythaemia vera (PV)](https://onco.cc/cancers/polycythaemia-vera/), [Primary myelofibrosis](https://onco.cc/cancers/primary-myelofibrosis/)
- journals: [Current hematologic malignancy reports](https://onco.cc/journals/current-hematologic-malignancy-reports/), [Leukemia & lymphoma](https://onco.cc/journals/leukemia-and-lymphoma/), [Leukemia research](https://onco.cc/journals/leukemia-research/)
- ideas: [Clearing the JAK2 clone in polycythaemia vera: interferon plus mutant-selective inhibitors as a route to treatment-free remission](https://onco.cc/ideas/idea-pv-clone-directed-therapy/)

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JSON: https://onco.cc/api/v1/entities/myeloproliferative-neoplasms.json