ArticleScientific reports2019
Retinoic acid and arsenic trioxide induce lasting differentiation and demethylation of target genes in APL cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- A phase 2 study of decitabine with or without carboplatin and arsenic trioxide in patients with MDS and AML.Blood neoplasia · 2025Trial
- Dynamic genetic and nongenetic RAS-pathway activation drives resistance to FLT3 and BCL2 inhibitor therapy.Blood · 2026Article
- The novel ETV6::RARA fusion gene, identified in acute promyelocytic leukemia, is sensitive to invitro all-tans retinoic acid and arsenic trioxide administrations.Annals of hematology · 2026Article
- Article
- Reversing the Warburg Effect: YW3-56 Induces Leukemia Differentiation via AKT-Mediated Glucose Metabolic Reprogramming.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Targeting CBP and p300: Emerging Anticancer Agents.Molecules (Basel, Switzerland) · 2024Review
- Combined treatment of All-trans retinoic acid with Tamoxifen suppresses ovarian cancer.Cancer chemotherapy and pharmacology · 2024Article
- Systems Biology for Drug Target Discovery in Acute Myeloid Leukemia.International journal of molecular sciences · 2024Article
- ATO Increases ROS Production and Apoptosis of Cells by Enhancing Calpain-Mediated Degradation of the Cancer Survival Protein TG2.International journal of molecular sciences · 2023Article
- Arsenic in medicine: past, present and future.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- Mechanistic update of Trisenox in blood cancer.Current research in pharmacology and drug discovery · 2023Review
- The Development and Clinical Applications of Oral Arsenic Trioxide for Acute Promyelocytic Leukaemia and Other Diseases.Pharmaceutics · 2022Review
- Antagonizing RARγ Drives Necroptosis of Cancer Stem Cells.International journal of molecular sciences · 2022Review
- All-trans retinoic acid (ATRA) regulates key genes in the RARG-TOP2B pathway and reduces anthracycline-induced cardiotoxicity.PloS one · 2022Article
- Dysregulation of Transglutaminase type 2 through GATA3 defines aggressiveness and Doxorubicin sensitivity in breast cancer.International journal of biological sciences · 2022Article
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Inhibition of the lncRNA Coded within Transglutaminase 2 Gene Impacts Several Relevant Networks in MCF-7 Breast Cancer Cells.Non-coding RNA · 2021Article
- MLL5 improves ATRA driven differentiation and promotes xenotransplant engraftment in acute promyelocytic leukemia model.Cell death & disease · 2021Article
- The RARγ Oncogene: An Achilles Heel for Some Cancers.International journal of molecular sciences · 2021Review
- Arsenic hexoxide has differential effects on cell proliferation and genome-wide gene expression in human primary mammary epithelial and MCF7 cells.Scientific reports · 2021Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Acute promyelocytic leukemia (APL) is characterized by arrested differentiation of promyelocytes. Patients treated with all-trans retinoic acid (ATRA) alone experience relapse, while patients treated with ATRA and arsenic trioxide (ATO) are often relapse-free. This suggests sustained changes have been elicited by the combination therapy. To understand the lasting effects of the combination therapy, we compared the effects of ATRA and ATO on NB4 and ATRA-resistant NB4-MR2 APL cells during treatment versus post treatment termination. After treatment termination, NB4 cells treated with ATRA or ATO reverted to non-differentiated cells, while combination-treated cells remained terminally differentiated. This effect was diminished in NB4-MR2 cells. This suggests combination treatment induced more permanent changes. Combination treatment induced higher expression of target genes (e.g., transglutaminase 2 and retinoic acid receptor beta), which in NB4 cells was sustained post treatment termination. To determine whether sustained epigenetic changes were responsible, we quantified the enrichment of histone modifications by chromatin immunoprecipitation, and CpG methylation by bisulfite-pyrosequencing. While ATRA and combination treatment induced similar histone acetylation enrichment, combination treatment induced greater demethylation of target genes, which was sustained. Therefore, sustained demethylation of target genes by ATRA and ATO combination treatment is associated with lasting differentiation and gene expression changes.
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