ArticleBlood2019
JAK2-mutant hematopoietic cells display metabolic alterations that can be targeted to treat myeloproliferative neoplasms.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- The proteomic architecture of clonal hematopoiesis: a systematic review of niche remodeling and multi-compartment predictors of malignant transformation.Frontiers in medicine · 2026Pooled it
- Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis.Nature communications · 2023Trial
- Differential responses to folic acid in an established keloid fibroblast cell line are mediated by JAK1/2 and STAT3.PloS one · 2021Trial
- Glucose transport dependency defines a therapeutic vulnerability in JAK2V617F-driven myeloproliferative neoplasms.Cell communication and signaling : CCS · 2026Article
- A paradigm shift in the treatment of patients with polycythemia vera. The initial early use of recombinant interferon-alpha.Leukemia · 2026Review
- Aggressive cholesterol lowering normalizes atherosclerosis regression in Jak2Journal of lipid research · 2026Article
- IRP1 deficiency alters mitochondrial metabolism and protects against metabolic syndrome pathologies.JCI insight · 2026Article
- Improving Immune Checkpoint Therapy in the Tumor Microenvironment by Targeting T Cell Metabolism.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Emerging concepts and novel mechanisms in organ fibrosis.NPJ Regenerative medicine · 2025Article
- Targeting mitochondrial dysfunction in myeloproliferative neoplasms: current strategies and future directions - a narrative review.Annals of medicine and surgery (2012) · 2025Review
- The Dual Role of Interferon Signaling in Myeloproliferative Neoplasms: Pathogenesis and Targeted Therapeutics.Cancers · 2025Review
- Metabolomic Profiling Reveals Distinct Signatures in Primary and Secondary Polycythemia.Metabolites · 2025Article
- JAK/STAT inhibition protects glucocorticoid receptor knockout mice from lethal malaria-induced hypoglycemia and hyperinflammation.EMBO molecular medicine · 2025Article
- Hypoxia-Induced Suppression of FAM99A and FAM99B Contributes to the Development and Glucose Metabolic Reprogramming of Hepatocellular Carcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Management of Myeloproliferative Neoplasms: An Integrative Approach.Journal of clinical medicine · 2025Review
- Malignant JAK-signaling: at the interface of inflammation and malignant transformation.Leukemia · 2025Review
- New approaches to standard of care in early-phase myeloproliferative neoplasms: can interferon-α alter the natural history of the disease?Haematologica · 2025Review
- Lactate accumulation promotes immunosuppression and fibrotic transformation of bone marrow microenvironment in myelofibrosis.Journal of translational medicine · 2025Article
- A stromal inflammasome Ras safeguard against Myc-driven lymphomagenesis.Nature immunology · 2025Article
- Diabetes mellitus, metformin, and the risk of MPN.Blood advances · 2024Article
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Authors and funding
30 authors at 12 institutions in 8 countries.
Funding
Abstract
Increased energy requirement and metabolic reprogramming are hallmarks of cancer cells. We show that metabolic alterations in hematopoietic cells are fundamental to the pathogenesis of mutant JAK2-driven myeloproliferative neoplasms (MPNs). We found that expression of mutant JAK2 augmented and subverted metabolic activity of MPN cells, resulting in systemic metabolic changes in vivo, including hypoglycemia, adipose tissue atrophy, and early mortality. Hypoglycemia in MPN mouse models correlated with hyperactive erythropoiesis and was due to a combination of elevated glycolysis and increased oxidative phosphorylation. Modulating nutrient supply through high-fat diet improved survival, whereas high-glucose diet augmented the MPN phenotype. Transcriptomic and metabolomic analyses identified numerous metabolic nodes in JAK2-mutant hematopoietic stem and progenitor cells that were altered in comparison with wild-type controls. We studied the consequences of elevated levels of Pfkfb3, a key regulatory enzyme of glycolysis, and found that pharmacological inhibition of Pfkfb3 with the small molecule 3PO reversed hypoglycemia and reduced hematopoietic manifestations of MPNs. These effects were additive with the JAK1/2 inhibitor ruxolitinib in vivo and in vitro. Inhibition of glycolysis by 3PO altered the redox homeostasis, leading to accumulation of reactive oxygen species and augmented apoptosis rate. Our findings reveal the contribution of metabolic alterations to the pathogenesis of MPNs and suggest that metabolic dependencies of mutant cells represent vulnerabilities that can be targeted for treating MPNs.
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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.