ArticleCell reports2013
Combined targeting of JAK2 and Bcl-2/Bcl-xL to cure mutant JAK2-driven malignancies and overcome acquired resistance to JAK2 inhibitors.
Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
87 citing papers in PubMed, 132 citations in OpenAlex.
- Trial
- Preliminary Safety and Efficacy of Navitoclax Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Patients With Myelofibrosis From the Multicenter, Open-Label, Phase 2 Study (REFINE).Hematological oncology · 2026Trial
- Addition of navitoclax to ruxolitinib for patients with myelofibrosis with progression or suboptimal response.Blood neoplasia · 2025Trial
- Addition of Navitoclax to Ongoing Ruxolitinib Therapy for Patients With Myelofibrosis With Progression or Suboptimal Response: Phase II Safety and Efficacy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- A phase 2 study of pracinostat combined with ruxolitinib in patients with myelofibrosis.Leukemia & lymphoma · 2019Trial
- Combination of p-STAT5, CRLF2 and copy number alterations as a potential indicator of a high-risk subgroup of acute lymphoblastic leukemia.Discover oncology · 2026Article
- Semi-Mechanistic PK/PD Modeling of Platelets and Spleen Volume With Navitoclax in Combination With Ruxolitinib in Patients With Myelofibrosis.CPT: pharmacometrics & systems pharmacology · 2026Article
- Review
- The Mechanisms of Resistance to JAK Inhibitors in Lymphoid Leukemias: A Scoping Review of Evidence from Preclinical Models and Case Reports.International journal of molecular sciences · 2025Article
- Efficacy of a novel BCL-xL degrader, DT2216, in preclinical models of JAK2-mutated post-MPN AML.Blood · 2025Article
- JAK2 in pediatric leukemia: mechanisms of pathogenesis and drug development - a narrative review.Annals of medicine and surgery (2012) · 2025Review
- Targeted Therapies in Myelofibrosis: Present Landscape, Ongoing Studies, and Future Perspectives.American journal of hematology · 2025Review
- Malignant JAK-signaling: at the interface of inflammation and malignant transformation.Leukemia · 2025Review
- Pharmacokinetics and Safety of Navitoclax in Hepatic Impairment.Clinical pharmacokinetics · 2025Article
- A novel application of XPO1 inhibition for the treatment of myelofibrosis.Blood neoplasia · 2024Review
- Tyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity.Nature communications · 2024Article
- Molecular Genetic Profile of Myelofibrosis: Implications in the Diagnosis, Prognosis, and Treatment Advancements.Cancers · 2024Review
- Targeted Therapy for MPNs: Going Beyond JAK Inhibitors.Current hematologic malignancy reports · 2023Review
- Novel therapeutics for myelofibrosis.Blood research · 2023Review
- Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 9 institutions in 4 countries.
Funding
Abstract
To design rational therapies for JAK2-driven hematological malignancies, we functionally dissected the key survival pathways downstream of hyperactive JAK2. In tumors driven by mutant JAK2, Stat1, Stat3, Stat5, and the Pi3k and Mek/Erk pathways were constitutively active, and gene expression profiling of TEL-JAK2 T-ALL cells revealed the upregulation of prosurvival Bcl-2 family genes. Combining the Bcl-2/Bcl-xL inhibitor ABT-737 with JAK2 inhibitors mediated prolonged disease regressions and cures in mice bearing primary human and mouse JAK2 mutant tumors. Moreover, combined targeting of JAK2 and Bcl-2/Bcl-xL was able to circumvent and overcome acquired resistance to single-agent JAK2 inhibitor treatment. Thus, inhibiting the oncogenic JAK2 signaling network at two nodal points, at the initiating stage (JAK2) and the effector stage (Bcl-2/Bcl-xL), is highly effective and provides a clearly superior therapeutic benefit than targeting just one node. Therefore, we have defined a potentially curative treatment for hematological malignancies expressing constitutively active JAK2.
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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.