ArticleBlood advances2019
Retinoic acid synergizes with the unfolded protein response and oxidative stress to induce cell death in FLT3-ITD+ AML.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- The ER Stress-related Gene Prognostic Signature for Predicting Chemosensitivity and Prognosis in AML.Recent patents on anti-cancer drug discovery · 2026Article
- Chronic ER Stress Triggers Cell-Surface Chaperones as the Therapeutic Targets of CAR Cells in Acute Myeloid Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- How to drug a leukemic stem cell: deciphering heterogeneity for better specificity.Blood neoplasia · 2025Review
- All-trans retinoic acid potentiates cell death induced by quizartinib in acute myeloid leukemia with FLT3-ITD mutations.Annals of hematology · 2024Article
- Review
- C/EBPα-p30 confers AML cell susceptibility to the terminal unfolded protein response and resistance to Venetoclax by activating DDIT3 transcription.Journal of experimental & clinical cancer research : CR · 2024Article
- HighOpen medicine (Warsaw, Poland) · 2024Article
- Retinoic acid and proteotoxic stress induce AML cell death overcoming stromal cell protection.Journal of experimental & clinical cancer research : CR · 2023Article
- NADPH oxidase mediated oxidative stress signaling in FLT3-ITD acute myeloid leukemia.Cell death discovery · 2023Review
- The Molecular Context of Oxidant Stress Response in Cancer Establishes ALDH1A1 as a Critical Target: What This Means for Acute Myeloid Leukemia.International journal of molecular sciences · 2023Review
- Combined scRNAseq and Bulk RNAseq Analysis to Reveal the Dual Roles of Oxidative Stress-Related Genes in Acute Myeloid Leukemia.Oxidative medicine and cellular longevity · 2023Article
- Circular RNAs Activity in the Leukemic Bone Marrow Microenvironment.Non-coding RNA · 2022Review
- Mitochondria inter-organelle relationships in cancer protein aggregation.Frontiers in cell and developmental biology · 2022Review
- 3-Ketodihydrosphingosine reductase maintains ER homeostasis and unfolded protein response in leukemia.Leukemia · 2022Article
- ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both?Biomolecules · 2021Review
- Unfolded Protein Response in Leukemia: From Basic Understanding to Therapeutic Opportunities.Trends in cancer · 2020Review
- Review
- VAS3947 Induces UPR-Mediated Apoptosis through Cysteine Thiol Alkylation in AML Cell Lines.International journal of molecular sciences · 2020Article
- Review
- Arsenic trioxide potentiates Gilteritinib-induced apoptosis in FLT3-ITD positive leukemic cells via IRE1a-JNK-mediated endoplasmic reticulum stress.Cancer cell international · 2020Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is often characterized by the expression of fusion or mutant proteins that cause impaired differentiation and enhanced proliferation and survival. The presence of mutant proteins prone to misfolding can render the cells sensitive to endoplasmic reticulum (ER) stress and oxidative stress that could otherwise be overcome. Here, we show that the triple combination of the differentiating agent retinoic acid (RA), the ER stress-inducing drug tunicamycin (Tm), and arsenic trioxide (ATO), able to generate oxidative stress, leads to the death of AML cell lines expressing fusion proteins involving the gene MLL and the internal tandem duplication (ITD) in the FLT3 tyrosine kinase receptor. Importantly, the combination of RA, Tm, and ATO decreased the colony-forming capacity of primary leukemic blasts bearing the FLT-ITD mutation without affecting healthy hematopoietic progenitor cells. We demonstrate in cell lines that combination of these drugs generates ER and oxidative stresses and impairs maturation and causes accumulation of FLT3 protein in the ER. Our data provide a proof of concept that low amounts of drugs that generate ER and oxidative stresses combined with RA could be an effective targeted therapy to hit AML cells characterized by MLL fusion proteins and FLT3-ITD mutation.
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Registered trials
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