ArticleBlood2014
Improved targeting of JAK2 leads to increased therapeutic efficacy in myeloproliferative neoplasms.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
73 citing papers in PubMed, 109 citations in OpenAlex.
- A phase 2 study of pracinostat combined with ruxolitinib in patients with myelofibrosis.Leukemia & lymphoma · 2019Trial
- Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias.Blood · 2015Trial
- JAK2V617F reprograms Hypoxia Inducible Factor-1 to induce a non-canonical hypoxia regulon in myeloproliferative neoplasms.Leukemia · 2026Article
- Article
- Oncolytic vesicular stomatitis virus alone or in combination with JAK inhibitors is effective against ovarian cancer.Molecular therapy. Oncology · 2024Article
- Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms.Cancer discovery · 2024Article
- Development of Resistance to Type II JAK2 Inhibitors in MPN Depends on AXL Kinase and Is Targetable.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Genomic and functional impact of Trp53 inactivation in JAK2V617F myeloproliferative neoplasms.Blood cancer journal · 2024Article
- Molecular biomarkers of leukemia: convergence-based drug resistance mechanisms in chronic myeloid leukemia and myeloproliferative neoplasms.Frontiers in pharmacology · 2024Review
- Article
- Recent advances in therapies for primary myelofibrosis.Faculty reviews · 2023Review
- JAK/BCL2 inhibition acts synergistically with LSD1 inhibitors to selectively target ETP-ALL.Leukemia · 2022Article
- Combination of ruxolitinib with ABT-737 exhibits synergistic effects in cells carrying concurrent JAK2Investigational new drugs · 2022Article
- Novel strategies for challenging scenarios encountered in managing myelofibrosis.Leukemia & lymphoma · 2022Article
- JAK2 inhibitor persistence in MPN: uncovering a central role of ERK activation.Blood cancer journal · 2022Review
- Review
- Article
- LigAdvisor: a versatile and user-friendly web-platform for drug design.Nucleic acids research · 2021Article
- Therapeutic Efficacy of Combined JAK1/2, Pan-PIM, and CDK4/6 Inhibition in Myeloproliferative Neoplasms.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Persistence of myelofibrosis treated with ruxolitinib: biology and clinical implications.Haematologica · 2021Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The discovery of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) led to clinical development of Janus kinase (JAK) inhibitors for treatment of MPN. These inhibitors improve constitutional symptoms and splenomegaly but do not significantly reduce mutant allele burden in patients. We recently showed that chronic exposure to JAK inhibitors results in inhibitor persistence via JAK2 transactivation and persistent JAK-signal transducer and activator of transcription signaling. We performed genetic and pharmacologic studies to determine whether improved JAK2 inhibition would show increased efficacy in MPN models and primary samples. Jak2 deletion in vivo led to profound reduction in disease burden not seen with JAK inhibitors, and deletion of Jak2 following chronic ruxolitinib therapy markedly reduced mutant allele burden. This demonstrates that JAK2 remains an essential target in MPN cells that survive in the setting of chronic JAK inhibition. Combination therapy with the heat shock protein 90 (HSP90) inhibitor PU-H71 and ruxolitinib reduced total and phospho-JAK2 and achieved more potent inhibition of downstream signaling than ruxolitinib monotherapy. Combination treatment improved blood counts, spleen weights, and reduced bone marrow fibrosis compared with ruxolitinib alone. These data suggest alternate approaches that increase JAK2 targeting, including combination JAK/HSP90 inhibitor therapy, are warranted in the clinical setting.
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What OpenQuestion holds
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.