Trial reportThe Journal of experimental medicine2016
Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia.
Trial report in The Journal of experimental medicine, 2016. 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.
- Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics.Frontiers in oncology · 2020Pooled it
- Randomized phase-III study of low-dose cytarabine and etoposide + /- all-trans retinoic acid in older unfit patients with NPM1-mutated acute myeloid leukemia.Scientific reports · 2023Trial
- All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study.Annals of hematology · 2016Trial
- Revisiting retinoic acid in AML therapy: mechanisms of action and rational combination strategies.British journal of cancer · 2026Review
- Alterations in 3D-DNA architecture drive unique leukemic profiles in IDH1- and DNMT3A-mutant acute myeloid leukemia.Leukemia · 2026Article
- Reawakening Differentiation Therapy in Acute Myeloid Leukemia: A Comprehensive Review of ATRA-Based Combination Strategies.Current oncology (Toronto, Ont.) · 2026Review
- Retinoic acid disrupts an NPM1c/ROS/SENP3/ARF oncogenic axis in acute myeloid leukemia.Leukemia · 2025Article
- Therapeutic implications of vitamin D in leukemia: mechanistic and clinical perspectives.Medical oncology (Northwood, London, England) · 2025Review
- Characteristics and Prognosis of "Acute Promyelocytic Leukemia-like" Nucleophosmin-1-Mutated Acute Myeloid Leukemia in a Retrospective Patient Cohort.Biomedicines · 2024Article
- Identification of leukemia stem cell subsets with distinct transcriptional, epigenetic and functional properties.Leukemia · 2024Article
- Acute Promyelocytic Leukemia, Retinoic Acid, and Arsenic: A Tale of Dualities.Cold Spring Harbor perspectives in medicine · 2024Review
- The Promise of Retinoids in the Treatment of Cancer: Neither Burnt Out Nor Fading Away.Cancers · 2023Review
- Vitamin D Derivatives in Acute Myeloid Leukemia: The Matter of Selecting the Right Targets.Nutrients · 2022Review
- A Novel Classification Model for Lower-Grade Glioma Patients Based on Pyroptosis-Related Genes.Brain sciences · 2022Article
- Evaluation of a DNA demethylating agent in combination with all-trans retinoic acid for IDH1-mutant gliomas.Neuro-oncology · 2022Article
- IDH1/2 Mutations in Cancer Stem Cells and Their Implications for Differentiation Therapy.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Review
- All-trans retinoic acid induces differentiation in primary acute myeloid leukemia blasts carrying an inversion of chromosome 16.International journal of hematology · 2022Article
- Metabolic adaptations in cancers expressing isocitrate dehydrogenase mutations.Cell reports. Medicine · 2021Review
- A Pin1/PML/P53 axis activated by retinoic acid inHaematologica · 2021Article
- Article
Corrections and comments
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Authors and funding
27 authors at 12 institutions in 3 countries.
Funding
Abstract
Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused by recurrent mutations, such as the isocitrate dehydrogenase (IDH) mutations found in 15% of AML patients. These mutations result in the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated by key transcription factors, particularly CEBPα, involved in myeloid differentiation and retinoid responsiveness. We show that treatment with all-trans retinoic acid (ATRA) at clinically achievable doses markedly enhanced terminal granulocytic differentiation in AML cell lines, primary patient samples, and a xenograft mouse model carrying mutant IDH1. Moreover, treatment with a cell-permeable form of 2-HG sensitized wild-type IDH1 AML cells to ATRA-induced myeloid differentiation, whereas inhibition of 2-HG production significantly reduced ATRA effects in mutant IDH1 cells. ATRA treatment specifically decreased cell viability and induced apoptosis of mutant IDH1 blasts in vitro. ATRA also reduced tumor burden of mutant IDH1 AML cells xenografted in NOD-Scid-IL2rγ(null)mice and markedly increased overall survival, revealing a potent antileukemic effect of ATRA in the presence of IDH1 mutation. This therapeutic strategy holds promise for this AML patient subgroup in future clinical studies.
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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.