Trial reportBlood cancer journal2022
The antileukemic activity of decitabine upon PML/RARA-negative AML blasts is supported by all-trans retinoic acid: in vitro and in vivo evidence for cooperation.
Trial report in Blood cancer journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00867672 (Prospective Randomized Multicenter Phase II Trial of Low-dose Decitabine), which is not on this map. Cited by 19 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.
Prospective Randomized Multicenter Phase II Trial of Low-dose Decitabine (DAC) Administered Alone or in Combination With the Histone Deacetylase Inhibitor Valproic Acid (VPA) and All-trans Retinoic Acid (ATRA) in Patients > 60 Years With Acute Myeloid Leukemia Who Are Ineligible for Induction Chemotherapy
Who cites it
19 citing papers in PubMed, 19 citations in OpenAlex.
- Trial
- Decitabine plus all-Haematologica · 2026Trial
- Impact of TP53 Mutation Status in Elderly AML Patients When Adding All-Trans Retinoic Acid or Valproic Acid to Decitabine.European journal of haematology · 2025Trial
- Activity of decitabine combined with all-Haematologica · 2023Trial
- Revisiting retinoic acid in AML therapy: mechanisms of action and rational combination strategies.British journal of cancer · 2026Review
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Pediatric acute myeloid leukemia tumor composition predicts patient outcomes at diagnosis and reveals mechanisms of resistance to chemotherapy.Research square · 2026Article
- Genome Agnostic Reprogramming of Acute Myelocytic Leukemia Hallmarks by Targeting Non-Oncogene Addictions with Azacitidine Plus Pioglitazone and All-Trans Retinoic Acid.International journal of molecular sciences · 2026Review
- Meta-analysis of clinical efficacy and safety of decitabine combined with CAG regimen in the treatment of acute myeloid leukemia in the elderly.Leukemia research reports · 2026Article
- Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation.Cell reports · 2025Article
- Characterization of Chemoresistant Cell Populations Improves Risk Stratification and Therapy Prediction in Pediatric AML.bioRxiv : the preprint server for biology · 2025Article
- RIG-I-Inducing Small Molecules Potently Inhibit HMA-Resistant AML Through Igniting the Overloaded dsRNA Arsenal.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A niche driven mechanism determines response and a mutation-independent therapeutic approach for myeloid malignancies.Cancer cell · 2025Article
- Genomic regions occupied by both RARα and VDR are involved in the convergence and cooperation of retinoid and vitamin D signaling pathways.Nucleic acids research · 2025Article
- Continued decitabine/all-trans retinoic acid treatment: extended complete remission in an elderly AML patient with multi-hit TP53 lesions and complex-monosomal karyotype.Clinical epigenetics · 2024Article
- All-trans retinoic acid in hematologic disorders: not just acute promyelocytic leukemia.Frontiers in pharmacology · 2024Review
- Article
- All-trans retinoic acid enhances the cytotoxic effect of decitabine on myelodysplastic syndromes and acute myeloid leukaemia by activating the RARα-Nrf2 complex.British journal of cancer · 2023Article
- Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment.Cancers · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prognosis of AML patients with adverse genetics, such as a complex, monosomal karyotype and TP53 lesions, is still dismal even with standard chemotherapy. DNA-hypomethylating agent monotherapy induces an encouraging response rate in these patients. When combined with decitabine (DAC), all-trans retinoic acid (ATRA) resulted in an improved response rate and longer overall survival in a randomized phase II trial (DECIDER; NCT00867672). The molecular mechanisms governing this in vivo synergism are unclear. We now demonstrate cooperative antileukemic effects of DAC and ATRA on AML cell lines U937 and MOLM-13. By RNA-sequencing, derepression of >1200 commonly regulated transcripts following the dual treatment was observed. Overall chromatin accessibility (interrogated by ATAC-seq) and, in particular, at motifs of retinoic acid response elements were affected by both single-agent DAC and ATRA, and enhanced by the dual treatment. Cooperativity regarding transcriptional induction and chromatin remodeling was demonstrated by interrogating the HIC1, CYP26A1, GBP4, and LYZ genes, in vivo gene derepression by expression studies on peripheral blood blasts from AML patients receiving DAC + ATRA. The two drugs also cooperated in derepression of transposable elements, more effectively in U937 (mutated TP53) than MOLM-13 (intact TP53), resulting in a "viral mimicry" response. In conclusion, we demonstrate that in vitro and in vivo, the antileukemic and gene-derepressive epigenetic activity of DAC is enhanced by ATRA.
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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.