Trial reportBlood2014
The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon α 2a target JAK2V617F-positive progenitor and stem cells.
Trial report in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed, 63 citations in OpenAlex.
- KT-253, a highly potent and selective MDM2 protein degrader, eliminates malignant myelofibrosis stem/progenitor cells.Leukemia · 2026Article
- MDM2 inhibitors in myeloid cancers: from basic biology to clinical use in myeloproliferative neoplasms.Leukemia · 2026Review
- Unraveling the role ofHemaSphere · 2026Review
- PPIL2 is a target of the JAK2/STAT5 pathway and promotes myeloproliferation via degradation of p53.The Journal of clinical investigation · 2025Article
- DNA Methylation in Ph-Negative Myeloproliferative Neoplasms: Prognostic Role and Therapeutic Implications.Current issues in molecular biology · 2025Review
- 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
- Article
- Targeted Therapy for MPNs: Going Beyond JAK Inhibitors.Current hematologic malignancy reports · 2023Review
- Recent advances in therapies for primary myelofibrosis.Faculty reviews · 2023Review
- Treating accelerated and blast phase myeloproliferative neoplasms: progress and challenges.Therapeutic advances in hematology · 2023Review
- Review
- Combined Drug Targeting of p53-dependent and -independent Pathways Depletes Myelofibrosis Hematopoietic Stem/Progenitor Cells.Leukemia · 2022Article
- Understanding Aberrant Signaling to Elude Therapy Escape Mechanisms in Myeloproliferative Neoplasms.Cancers · 2022Review
- Integration of Molecular Information in Risk Assessment of Patients with Myeloproliferative Neoplasms.Cells · 2021Review
- Review
- Review
- Distinct effects of V617F and exon12-mutated JAK2 expressions on erythropoiesis in a human induced pluripotent stem cell (iPSC)-based model.Scientific reports · 2021Article
- JAK2V617F myeloproliferative neoplasm eradication by a novel interferon/arsenic therapy involves PML.The Journal of experimental medicine · 2021Article
- Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The Philadelphia chromosomal-negative chronic myeloproliferative neoplasms (MPNs) originate at the level of the hematopoietic stem cell (HSC). The protracted clinical course of the MPNs has limited the use of potentially toxic treatment modalities, which may eliminate the responsible malignant clone. Treatment with low doses of RG7112, an orally available small-molecule inhibitor of p53-MDM2, both alone and combined with pegylated interferon α 2a (Peg-IFNα 2a), significantly decreased MPN colony-forming unit-granulocyte macrophage and burst-forming unit-erythroid numbers and preferentially eliminated the total number of JAKV617F(+) MPN hematopoietic progenitor cells. The effects of RG7112 and Peg-IFNα 2a on MPN progenitor cells were dependent on blocking p53-MDM2 interactions and activating the p53 pathway, thereby increasing MPN CD34(+) cell apoptosis. Treatment of polycythemia vera (PV) and primary myelofibrosis (PMF) CD34(+) cells with low doses of RG7112 and Peg-IFNα 2a before their transplantation into immune-deficient mice decreased the degree of donor-derived chimerism as well as the JAK2V617F allele burden, indicating that these drugs can each alone or in combination deplete MPN HSCs. These results provide a rationale for the use of combinations of low doses of RG7112 and Peg-IFNα 2a for the treatment of PV or PMF patients with the intent of altering their natural history.
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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 Socratic graph.