ArticleBlood2009
Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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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
84 citing papers in PubMed, 177 citations in OpenAlex.
- A phase 2 study of pracinostat combined with ruxolitinib in patients with myelofibrosis.Leukemia & lymphoma · 2019Trial
- Trial
- Selective JAK2 inhibition by TG101209 reprograms macrophage polarization and alleviates acute lung injury.Frontiers in immunology · 2026Article
- Assessing the selective impact of histone modifying drugs on adenoid cystic carcinoma cells and their stem cell counterparts.BMC cancer · 2025Article
- Review
- Combination of JAKi and HDACi Exerts Antiangiogenic Potential in Cutaneous T-Cell Lymphoma.Cancers · 2024Article
- Molecular Genetic Profile of Myelofibrosis: Implications in the Diagnosis, Prognosis, and Treatment Advancements.Cancers · 2024Review
- Recent advances in therapies for primary myelofibrosis.Faculty reviews · 2023Review
- Novel strategies for challenging scenarios encountered in managing myelofibrosis.Leukemia & lymphoma · 2022Article
- Article
- Review
- The JAK2 inhibitor TG101209 exhibits anti-tumor and chemotherapeutic sensitizing effects on Burkitt lymphoma cells by inhibiting the JAK2/STAT3/c-MYB signaling axis.Cell death discovery · 2021Article
- Article
- Mathematical model of STAT signalling pathways in cancer development and optimal control approaches.Royal Society open science · 2021Article
- Novel Pathophysiological Mechanisms of Thrombosis in Myeloproliferative Neoplasms.Current hematologic malignancy reports · 2021Review
- Emerging agents and regimens for polycythemia vera and essential thrombocythemia.Biomarker research · 2021Review
- Epigenetic Dysregulation of Myeloproliferative Neoplasms.Hematology/oncology clinics of North America · 2021Review
- Shifting the paradigm in treating multi-factorial diseases: polypharmacological co-inhibitors of HDAC6.RSC medicinal chemistry · 2021Review
- Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.International journal of molecular sciences · 2021Review
- Finding a Jill for JAK: Assessing Past, Present, and Future JAK Inhibitor Combination Approaches in Myelofibrosis.Cancers · 2020Review
24 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
16 authors at 3 institutions in 1 country.
Funding
Abstract
The mutant JAK2V617F tyrosine kinase (TK) is present in the majority of patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). JAK2V617F activates downstream signaling through the signal transducers and activators of transcription (STAT), RAS/mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3 (PI3)/AKT pathways, conferring proliferative and survival advantages in the MPN hematopoietic progenitor cells (HPCs). Treatment with the pan-histone deacetylase (HDAC) inhibitor panobinostat (PS) is known to inhibit the chaperone function of heat shock protein 90, as well as induce growth arrest and apoptosis of transformed HPCs. Here, we demonstrate that PS treatment depletes the autophosphorylation, expression, and downstream signaling of JAK2V617F. Treatment with PS also disrupted the chaperone association of JAK2V617F with hsp90, promoting proteasomal degradation of JAK2V617F. PS also induced apoptosis of the cultured JAK2V617F-expressing human erythroleukemia HEL92.1.7 and Ba/F3-JAK2V617F cells. Treatment with the JAK2 TK inhibitor TG101209 attenuated JAK2V617F autophosphorylation and induced apoptosis of HEL92.1.7 and Ba/F3-JAK2V617F cells. Cotreatment with PS and TG101209 further depleted JAK/STAT signaling and synergistically induced apoptosis of HEL92.1.7 and Ba/F3-JAK2V617F cells. Cotreatment with TG101209 and PS exerted greater cytotoxicity against primary CD34(+) MPN cells than normal CD34(+) HPCs. These in vitro findings suggest combination therapy with HDAC and JAK2V617F inhibitors is of potential value for the treatment of JAK2V617F-positive MPN.
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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.