ArticleCancer discovery2015
JAK-STAT pathway activation in malignant and nonmalignant cells contributes to MPN pathogenesis and therapeutic response.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 223 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
223 citing papers in PubMed, 306 citations in OpenAlex.
- Safety and efficacy of fedratinib, a selective oral inhibitor of Janus kinase-2 (JAK2), in patients with myelofibrosis and low pretreatment platelet counts.British journal of haematology · 2022Trial
- Updated results of the placebo-controlled, phase III JAKARTA trial of fedratinib in patients with intermediate-2 or high-risk myelofibrosis.British journal of haematology · 2021Trial
- Fedratinib in patients with myelofibrosis previously treated with ruxolitinib: An updated analysis of the JAKARTA2 study using stringent criteria for ruxolitinib failure.American journal of hematology · 2020Trial
- Ruxolitinib for symptom control in patients with chronic lymphocytic leukaemia: a single-group, phase 2 trial.The Lancet. Haematology · 2017Trial
- Anti-Platelet Factor 4/Heparin Antibody Formation Occurs Endogenously and at Unexpected High Frequency in Polycythemia Vera.BioMed research international · 2017Trial
- Fufang Huangbo Formula mitigates myeloproliferative neoplasms by activating p53/p21 signaling axis and inhibiting STAT3 and NF-κB signaling pathways.Pharmaceutical science advances · 2026Article
- Megakaryocytes in myelofibrosis: mechanisms of fibrotic niche remodeling and therapeutic implications.Biomarker research · 2026Review
- Molecular Response, Event-Free Survival, and Treatment-Free Remission in Myeloproliferative Neoplasms: Update and Review with Insights from MPN Asia 2026.Current hematologic malignancy reports · 2026Review
- Increased Mast Cell Numbers in Bone Marrow of Patients with Myeloproliferative Neoplasms and PruritusTurkish journal of haematology : official journal of Turkish Society of Haematology · 2026Article
- Resolving diagnostic uncertainty in rare MPL and CALR variants: A practical framework for the haematology clinic.British journal of haematology · 2026Article
- Inflammatory and Immune Microenvironment in Myeloproliferative Neoplasms: Pathogenic Mechanisms and Therapeutic Opportunities.Cancers · 2026Review
- The bidirectional relationship betweenHemaSphere · 2026Article
- Preserving thrombosis and life years in polycythemia vera: start by reading the biology of the disease.Haematologica · 2026Article
- MDM2 inhibitors in myeloid cancers: from basic biology to clinical use in myeloproliferative neoplasms.Leukemia · 2026Review
- Positive and Negative Cardiovascular Effects of JAK Inhibitors in Inflammation.ACR open rheumatology · 2026Review
- Multi-Compartment Transcriptomics Identifies a Persistent Inflammatory Program and a Network-Derived Diagnostic Signature in Polycythemia Vera.International journal of molecular sciences · 2026Article
- Clonal hematopoiesis in the pathogenesis of non-hematologic diseases with therapeutic potential.Cancer cell international · 2026Review
- Platelets Outperform Leukocytes in Transcriptomic Liquid Biopsy Profiling of Myeloproliferative Neoplasms.bioRxiv : the preprint server for biology · 2026Article
- Toward new therapy end points in polycythemia vera: targeting clonal and inflammatory pathways.Blood advances · 2026Review
- Bone Metastasis in Estrogen Receptor-Positive Breast Cancer: Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2026Review
163 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledThe identification of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) has led to the clinical development of JAK kinase inhibitors, including ruxolitinib. Ruxolitinib reduces splenomegaly and systemic symptoms in myelofibrosis and improves overall survival; however, the mechanism by which JAK inhibitors achieve efficacy has not been delineated. Patients with MPN present with increased levels of circulating proinflammatory cytokines, which are mitigated by JAK inhibitor therapy. We sought to elucidate mechanisms by which JAK inhibitors attenuate cytokine-mediated pathophysiology. Single-cell profiling demonstrated that hematopoietic cells from myelofibrosis models and patient samples aberrantly secrete inflammatory cytokines. Pan-hematopoietic Stat3 deletion reduced disease severity and attenuated cytokine secretion, with similar efficacy as observed with ruxolitinib therapy. In contrast, Stat3 deletion restricted to MPN cells did not reduce disease severity or cytokine production. Consistent with these observations, we found that malignant and nonmalignant cells aberrantly secrete cytokines and JAK inhibition reduces cytokine production from both populations. SIGNIFICANCE: Our results demonstrate that JAK-STAT3-mediated cytokine production from malignant and nonmalignant cells contributes to MPN pathogenesis and that JAK inhibition in both populations is required for therapeutic efficacy. These findings provide novel insight into the mechanisms by which JAK kinase inhibition achieves therapeutic efficacy in MPNs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.