ArticleLeukemia2017
BET protein bromodomain inhibitor-based combinations are highly active against post-myeloproliferative neoplasm secondary AML cells.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed, 89 citations in OpenAlex.
- A phase 1/2 study of ruxolitinib and decitabine in patients with post-myeloproliferative neoplasm acute myeloid leukemia.Leukemia · 2020Trial
- PIM1 in myeloproliferative neoplasms: potential pathogenic and therapeutic implications.Leukemia · 2026Review
- SOHO State of the Art Updates and Next Questions | Challenging Scenarios in the Management of Myeloproliferative Neoplasms.Clinical lymphoma, myeloma & leukemia · 2025Review
- Prevention and treatment of transformation of myeloproliferative neoplasms to acute myeloid leukemia.Haematologica · 2025Review
- Article
- Myelofibrosis: Timing of Transplantation and Management of Splenomegaly.Advances in experimental medicine and biology · 2025Review
- Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era.Blood advances · 2024Article
- BET in hematologic tumors: Immunity, pathogenesis, clinical trials and drug combinations.Genes & diseases · 2023Review
- Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Targeted Therapy for MPNs: Going Beyond JAK Inhibitors.Current hematologic malignancy reports · 2023Review
- SOHO State of the Art Updates and Next Questions: Novel Therapeutic Strategies in Development for Myelofibrosis.Clinical lymphoma, myeloma & leukemia · 2023Review
- Hitting the brakes on accelerated and blast-phase myeloproliferative neoplasms: current and emerging concepts.Hematology. American Society of Hematology. Education Program · 2022Article
- Acute Myeloid Leukemia Following Myeloproliferative Neoplasms: A Review of What We Know, What We Do Not Know, and Emerging Treatment Strategies.Journal of hematology · 2022Review
- UM171 cooperates with PIM1 inhibitors to restrict HSC expansion markers and suppress leukemia progression.Cell death discovery · 2022Article
- Review
- Novel strategies for challenging scenarios encountered in managing myelofibrosis.Leukemia & lymphoma · 2022Article
- PD-L1 overexpression correlates with JAK2-V617F mutational burden and is associated with 9p uniparental disomy in myeloproliferative neoplasms.American journal of hematology · 2022Article
- The BET bromodomain inhibitor ZEN-3365 targets the Hedgehog signaling pathway in acute myeloid leukemia.Annals of hematology · 2021Article
- Evolving Therapeutic Approaches for Older Patients with Acute Myeloid Leukemia in 2021.Cancers · 2021Review
- JAK Be Nimble: Reviewing the Development of JAK Inhibitors and JAK Inhibitor Combinations for Special Populations of Patients with Myelofibrosis.Journal of immunotherapy and precision oncology · 2021Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Myeloproliferative neoplasms with myelofibrosis (MPN-MF) demonstrate constitutive activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling that responds to treatment with the JAK1 and 2 kinase inhibitor (JAKi) ruxolitinib. However, MPN-MF often progresses (~20%) to secondary acute myeloid leukemia (sAML), where standard induction chemotherapy or ruxolitinib is relatively ineffective, necessitating the development of novel therapeutic approaches. In the present studies, we demonstrate that treatment with BET (bromodomain and extraterminal) protein inhibitor (BETi), for example, JQ1, inhibits growth and induces apoptosis of cultured and primary, patient-derived (PD), post-MPN sAML blast progenitor cells. Reverse-phase protein array, mass-cytometry and Western analyses revealed that BETi treatment attenuated the protein expressions of c-MYC, p-STAT5, Bcl-xL, CDK4/6, PIM1 and IL-7R, whereas it concomitantly induced the levels of HEXIM1, p21 and BIM in the sAML cells. Co-treatment with BETi and ruxolitinib synergistically induced apoptosis of cultured and PD sAML cells, as well as significantly improved survival of immune-depleted mice engrafted with human sAML cells. Although BETi or heat shock protein 90 inhibitor (HSP90i) alone exerted lethal activity, cotreatment with BETi and HSP90i was synergistically lethal against the ruxolitinib-persister or ruxolitinib-resistant sAML cells. Collectively, these findings further support in vivo testing of BETi-based combinations with JAKi and HSP90i against post-MPN sAML cells.
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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.