ArticleLeukemia2015
Pharmacological targeting of miR-155 via the NEDD8-activating enzyme inhibitor MLN4924 (Pevonedistat) in FLT3-ITD acute myeloid leukemia.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- The relationship of miR-155 host gene polymorphism in the susceptibility of cancer: a systematic review and meta-analysis.Frontiers in genetics · 2025Pooled it
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Investigating autophagy and miRNAs as therapeutic targets in leukemia.Discover oncology · 2026Review
- Article
- The crosstalk between MiRNAs and autophagy in leukemia: mechanisms and therapeutic insights.Discover oncology · 2025Review
- Functions, mechanisms, and therapeutic implications of noncoding RNA in acute myeloid leukemia.Fundamental research · 2025Review
- MircoRNAs predict and modulate responses to chemotherapy in leukemic patients.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Immune checkpoints and ncRNAs: pioneering immunotherapy approaches for hematological malignancies.Cancer cell international · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- A phase I trial of pevonedistat in combination with ruxolitinib for the treatment of myelofibrosis.Therapeutic advances in hematology · 2024Article
- Shikonin Exerts an Antileukemia Effect against FLT3-ITD Mutated Acute Myeloid Leukemia Cells via Targeting FLT3 and Its Downstream Pathways.Acta haematologica · 2024Article
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- Targeting neddylation as a novel approach to lung cancer treatment (Review).International journal of oncology · 2023Review
- MLN4924 Promotes Self-Renewal of Limbal Stem Cells and Ocular Surface Restoration.Journal of personalized medicine · 2023Article
- Major roles of the circadian clock in cancer.Cancer biology & medicine · 2023Review
- Article
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- Inhibition of NEDD8 NEDDylation induced apoptosis in acute myeloid leukemia cells via p53 signaling pathway.Bioscience reports · 2022Article
- Pevonedistat and azacitidine upregulate NOXA (PMAIP1) to increase sensitivity to venetoclax in preclinical models of acute myeloid leukemia.Haematologica · 2022Article
- Pevonedistat targets malignant cells in myeloproliferative neoplasms in vitro and in vivo via NFκB pathway inhibition.Blood advances · 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
24 authors at 7 institutions in 1 country.
Funding
Abstract
High levels of microRNA-155 (miR-155) are associated with poor outcome in acute myeloid leukemia (AML). In AML, miR-155 is regulated by NF-κB, the activity of which is, in part, controlled by the NEDD8-dependent ubiquitin ligases. We demonstrate that MLN4924, an inhibitor of NEDD8-activating enzyme presently being evaluated in clinical trials, decreases binding of NF-κB to the miR-155 promoter and downregulates miR-155 in AML cells. This results in the upregulation of the miR-155 targets SHIP1, an inhibitor of the PI3K/Akt pathway, and PU.1, a transcription factor important for myeloid differentiation, leading to monocytic differentiation and apoptosis. Consistent with these results, overexpression of miR-155 diminishes MLN4924-induced antileukemic effects. In vivo, MLN4924 reduces miR-155 expression and prolongs the survival of mice engrafted with leukemic cells. Our study demonstrates the potential of miR-155 as a novel therapeutic target in AML via pharmacologic interference with NF-κB-dependent regulatory mechanisms. We show the targeting of this oncogenic microRNA with MLN4924, a compound presently being evaluated in clinical trials in AML. As high miR-155 levels have been consistently associated with aggressive clinical phenotypes, our work opens new avenues for microRNA-targeting therapeutic approaches to leukemia and cancer patients.
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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.