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The signalling enzyme that tells marrow cells to make red cells and platelets; a single mutation (V617F) leaves it switched on in most myeloproliferative neoplasms. This dossier gathers the 6 products (5 approved), 27 trials, 3 pathways and 1 resistance route in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
JAK2 is a non-receptor tyrosine kinase with a pseudokinase (JH2) domain that normally restrains the kinase (JH1); V617F in JH2 relieves autoinhibition, causing cytokine-independent STAT5/MAPK/PI3K signalling and erythroid/megakaryocytic expansion.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Myeloproliferative neoplasms | 60-95% | JAK2 V617F by subtype | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| V617F 617 | Activating | About 95% of polycythaemia vera and 50 to 60% of essential thrombocythaemia and primary myelofibrosis | Pseudokinase mutation that releases auto-inhibition. The approved JAK inhibitors block the kinase domain and are not mutation-selective; V617F-selective inhibitors are in development. | - | Baxter et al., Lancet 2005 | |
| Exon 12 (N542_E543del, K539L) 540 | Activating | About 3% of polycythaemia vera | V617F-negative PV; same drugs. | - | COSMIC: JAK2 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: COSMIC: JAK2.
| Modality | Approved | Phase 1 |
|---|---|---|
| Small molecule 4 | - | |
| Antibody 1 | - | |
| Long-acting mono-pegylated interferon alfa 1 | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
MANIFEST-2 NCT04603495 | 3 | Mixed | JAK inhibitor-naive myelofibrosis: ruxolitinib with the BET inhibitor pelabresib or placebo | Pelabresib plus ruxolitinib roughly doubled the week-24 spleen volume response over ruxolitinib alone; the symptom endpoint did not reach significance. | |
MOMENTUM NCT04173494 | 3 | Positive | Symptomatic, anaemic myelofibrosis previously treated with a JAK inhibitor: momelotinib against danazol | Momelotinib improved symptom response, transfusion independence and spleen response compared with danazol; approved in September 2023. | |
PROUD-PV and CONTINUATION-PV NCT01949805 | 3 | Positive | Polycythaemia vera needing cytoreduction: ropeginterferon alfa-2b versus hydroxyurea, with long-term follow-up | By 36 months, complete haematological response with improved disease burden and molecular response were both more frequent with ropeginterferon than hydroxyurea. | |
RESPONSE-2 NCT02038036 | 3 | Positive | Hydroxyurea-resistant or intolerant polycythaemia vera without splenomegaly: ruxolitinib versus best available therapy | Haematocrit control at week 28: 62% vs 19%. | |
RESPONSE NCT01243944 | 3 | Positive | Polycythaemia vera resistant to or intolerant of hydroxyurea, with an enlarged spleen: ruxolitinib versus best available therapy | Composite response at week 32: 21% vs 1%; haematocrit control 60% vs 20%. | |
COMFORT-I NCT00952289 | 3 | Positive | Intermediate-2 or high-risk primary myelofibrosis, post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis: twice-daily oral ruxolitinib or placebo, with spleen volume by MRI at 24 weeks as the primary endpoint | Spleen volume reduction of 35 percent or more at 24 weeks in 41.9 percent of patients on ruxolitinib against 0.7 percent on placebo; approved in the United States in November 2011. | |
COMFORT-II NCT00934544 | 3 | Positive | Intermediate-2 or high-risk primary myelofibrosis, post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis: open-label ruxolitinib against best available therapy chosen by the physician, with spleen volume at 48 weeks as the primary endpoint | Spleen volume reduction of at least 35 percent at week 48 in 28 percent of patients on ruxolitinib against 0 percent on best available therapy; European approval in 2012. | |
| PT-1 (Primary Thrombocythaemia 1) | 3 | Positive | High-risk essential thrombocythaemia: hydroxyurea plus aspirin versus anagrelide plus aspirin | Composite of thrombosis, serious haemorrhage or vascular death more frequent with anagrelide (odds ratio 1.57); more arterial clots, bleeding and myelofibrosis on anagrelide. | |
| 3 | Active | A Phase IIIb, Randomized, Open-Label, Parallel Group, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Two Dosing Regimens of Ropeginterferon Alfa-2b-njft (P1101) in Adult Patients With Polycythemia Vera (PV) | - | ||
| 3 | Recruiting | Extension Study of P1101 in Japanese Patients Who Have Completed Phase 2 Single Arm Study in Polycythemia Vera (PV) Patients (Study A19-201) or Phase 3 Study in Essential Thrombocythemia (ET) Patients (Study P1101 ET) | - | ||
| 3 | Active | A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase III Study to Assess Efficacy and Safety of Ropeginterferon Alfa-2b (P1101) in Adult Patients With Pre-fibrotic/Early Primary Myelofibrosis (PMF) or Overt PMF at Low or Intermediate-1 Risk According to DIPSS Plus (HOPE-PMF): The Core Study and Its Extension Study | - | ||
| 3 | Active | A Phase 3, Open-Label, Multicenter, Randomized, Active-controlled Study to Assess PK and Compare the Efficacy, Safety, and Tolerability of P1101 vs Anagrelide as 2nd Line Therapy for Essential Thrombocythemia (SURPASS ET): The Core Study and Its Extension Study. | - | ||
| 3 | Active | A Phase 1/3 Study to Evaluate Efficacy and Safety of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Ruxolitinib in Treatment-naïve Patients With Myelofibrosis | - | ||
| 2 | - | Fostamatinib as a Single Agent or in Combination With Ruxolitinib for Treatment of Patients With Myelofibrosis With Severe Thrombocytopenia | - | ||
| MAJIC-PV | 2 | Positive | Hydroxyurea-resistant or intolerant polycythaemia vera: ruxolitinib versus best available therapy | Complete response within 1 year: 43% vs 26%; complete response associated with better event-free survival. | |
Low-PV NCT03003325 | 2 | Positive | Low-risk polycythaemia vera: ropeginterferon alfa-2b plus phlebotomy versus phlebotomy alone | Haematocrit at or below 45% without progression at 12 months: 84% vs 60%. | |
KEYNOTE-170 NCT02576990 | 2 | Positive | Relapsed or refractory primary mediastinal large B-cell lymphoma after autologous transplant, or ineligible for it after two or more lines: pembrolizumab monotherapy | Objective response rate 45%, complete response 13%, in 53 patients with relapsed or refractory disease; FDA accelerated approval June 2018. | |
| MAJIC-ET | 2 | Negative | Hydroxyurea-resistant or intolerant essential thrombocythaemia: ruxolitinib versus best available therapy | Complete response within 1 year 46.6% (ruxolitinib) vs 44.2% (best available therapy), not significant; no difference in clots, bleeding or transformation at 2 years. | |
| 2 | Active | A Single-arm, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Ropeginterferon Alfa-2b-njft (P1101) in Adult Patients With Essential Thrombocythemia | - | ||
| 2 | Active | A Phase II Single-Arm Multicenter Study to Access Efficacy and Safety of P1101 in Chinese Polycythemia Vera Patients Who Are Intolerant or Resistance to Hydroxyurea | - | ||
AALL1521 NCT02723994 | 2 | Completed | Children and young adults with newly diagnosed high-risk Philadelphia chromosome-like B-cell acute lymphoblastic leukaemia carrying a CRLF2 rearrangement or a JAK pathway mutation: the JAK1 and JAK2 inhibitor ruxolitinib added to post-induction chemotherapy, in a dose-finding part and an efficacy part with three-year event-free survival as the endpoint | - | |
| 2 | Active | An Open-Label, Multicenter, Rollover Study to Enable Continued Treatment Access for Subjects Previously Enrolled in Studies of Ruxolitinib | - | ||
| 2 | Active | A Two-Part, Randomized, Open-label, Multicenter, Phase 2a/2b Study of the Efficacy, Safety, and Pharmacokinetics of KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera | - | ||
| 2 | Recruiting | A Randomized Phase 2 Study of Pacritinib vs. Hydroxyurea in Patients With Advanced Proliferative Chronic Myelomonocytic Leukemia | - | ||
| 2 | Active | A Phase 2, Open-Label, Multicenter, Rollover Study to Provide Continued Treatment for Participants With B-Cell Malignancies Previously Enrolled in Studies of Parsaclisib (INCB050465) | - | ||
| 1/2 | Active | A Phase 1b/2 Study of BMS-986158 Monotherapy and in Combination With Either Ruxolitinib or Fedratinib in Participants With DIPSS-Intermediate or High Risk Myelofibrosis | - | ||
| 1/2 | Recruiting | PRISM: Phase 1b of Retifanlimab and Ruxolitinib In Solid Malignancies Progressing on Prior Checkpoint Inhibition | - |
The alteration is near-universal but graded, and higher-level copy gain predicted longer progression-free survival, so the patients with least of it do least well.
This KEGG map shows how chemicals in tobacco smoke, industrial pollutants, plastics and hormones cause cancer without directly damaging DNA: they switch on receptors that drive growth signalling. It matters because these routes explain part of the cancer burden from smoking, dioxins and hormone exposure, and several of the receptors are druggable.
Which nodes have drugs →Tumours recruit the body's repair cells, fibroblasts, and keep them in wound-healing mode forever. The scar tissue they lay down (desmoplasia) squeezes blood vessels shut, walls out immune cells, stiffens the tissue in a way that itself tells cancer cells to grow, and is why pancreatic cancer is so hard to treat.
Which nodes have drugs →This KEGG map shows the order of genetic hits that turn normal pancreatic duct cells into ductal adenocarcinoma: KRAS mutation first, then loss of the p16 brake, then loss of TP53, SMAD4 and BRCA2. It matters because nearly every pancreatic cancer is driven by KRAS, which until recently had no drug.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"JAK2" OR ABSTRACT:"JAK2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about JAK2, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/jak2.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/jak2.json. Licence CC BY-NC 4.0.