ArticleBlood2012
Combination treatment in vitro with Nutlin, a small-molecule antagonist of MDM2, and pegylated interferon-α 2a specifically targets JAK2V617F-positive polycythemia vera cells.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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
40 citing papers in PubMed, 66 citations in OpenAlex.
- The MDM2 antagonist idasanutlin in patients with polycythemia vera: results from a single-arm phase 2 study.Blood advances · 2022Trial
- Trial
- Fufang Huangbo Formula mitigates myeloproliferative neoplasms by activating p53/p21 signaling axis and inhibiting STAT3 and NF-κB signaling pathways.Pharmaceutical science advances · 2026Article
- Immunomodulatory role of megakaryocytes in the hematopoietic niche of myeloproliferative neoplasms.Haematologica · 2026Article
- MDM2 inhibitors in myeloid cancers: from basic biology to clinical use in myeloproliferative neoplasms.Leukemia · 2026Review
- Unraveling the role ofHemaSphere · 2026Review
- Advances in polycythemia vera treatment with targeted therapies and clinical trials.Discover oncology · 2025Review
- Targeting the MDM2-MDM4 interaction interface reveals an otherwise therapeutically active wild-type p53 in colorectal cancer.Molecular oncology · 2025Article
- New approaches to standard of care in early-phase myeloproliferative neoplasms: can interferon-α alter the natural history of the disease?Haematologica · 2025Review
- Impact of Phlebotomy on Quality of Life in Low-Risk Polycythemia Vera.Journal of clinical medicine · 2024Review
- Genomic and functional impact of Trp53 inactivation in JAK2V617F myeloproliferative neoplasms.Blood cancer journal · 2024Article
- MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation.Biomedicines · 2023Review
- Targeted Therapy for MPNs: Going Beyond JAK Inhibitors.Current hematologic malignancy reports · 2023Review
- Treating accelerated and blast phase myeloproliferative neoplasms: progress and challenges.Therapeutic advances in hematology · 2023Review
- Advances in Risk Stratification and Treatment of Polycythemia Vera and Essential Thrombocythemia.Current hematologic malignancy reports · 2022Review
- Novel Therapies in Myelofibrosis: Beyond JAK Inhibitors.Current hematologic malignancy reports · 2022Review
- Single-cell analysis reveals selection of TP53-mutated clones after MDM2 inhibition.Blood advances · 2022Article
- Novel treatments for myelofibrosis: beyond JAK inhibitors.International journal of hematology · 2022Review
- Treatment options and pregnancy management for patients with PV and ET.International journal of hematology · 2022Review
- Combined Drug Targeting of p53-dependent and -independent Pathways Depletes Myelofibrosis Hematopoietic Stem/Progenitor Cells.Leukemia · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Interferon (IFN-α) is effective therapy for polycythemia vera (PV) patients, but it is frequently interrupted because of adverse events. To permit the long-term use of IFN, we propose combining low doses of IFN with Nutlin-3, an antagonist of MDM2, which is also capable of promoting PV CD34(+) cell apoptosis. Combination treatment with subtherapeutic doses of Peg IFN-α 2a and Nutlin-3 inhibited PV CD34(+) cell proliferation by 50% while inhibiting normal CD34(+) cells by 30%. Combination treatment with Nutlin-3 and Peg IFN-α 2a inhibited PV colony formation by 55%-90% while inhibiting normal colony formation by 22%-30%. The combination of these agents also decreased the proportion of JAK2V617F-positive hematopoietic progenitor cells in 6 PV patients studied. Treatment with low doses of Peg IFN-α 2a combined with Nutlin-3 increased phospho-p53 and p21 protein levels in PV CD34(+) cells and increased the degree of apoptosis. These 2 reagents affect the tumor suppressor p53 through different pathways with Peg IFN-α 2a activating p38 MAP kinase and STAT1, leading to increased p53 transcription, whereas Nutlin-3 prevents the degradation of p53. These data suggest that treatment with low doses of both Nutlin-3 combined with Peg IFN-α 2a can target PV hematopoietic progenitor cells, eliminating the numbers of malignant hematopoietic progenitor 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.