ArticlePloS one2015
Comparison of newly diagnosed and relapsed patients with acute promyelocytic leukemia treated with arsenic trioxide: insight into mechanisms of resistance.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- A phase II study evaluating the role of bortezomib in the management of relapsed acute promyelocytic leukemia treated upfront with arsenic trioxide.Cancer medicine · 2020Trial
- Patient-derived xenografts faithfully replicated clinical outcome in a phase II co-clinical trial of arsenic trioxide in relapsed small cell lung cancer.Journal of translational medicine · 2016Trial
- PML::RARα+ myeloid cells display metabolic alterations that can be targeted to treat resistant/relapse acute promyelocytic leukemias.Leukemia · 2025Article
- Microvesicle inhibition enhances the therapeutic effects of ATRA in acute promyelocytic leukemia cells via changes in miRNAs: the promising antileukemic potential of imipramine.Clinical and experimental medicine · 2025Article
- Galectin-3 Release in the Bone Marrow Microenvironment Promotes Drug Resistance and Relapse in Acute Myeloid Leukemia.Life (Basel, Switzerland) · 2025Review
- PML mutants from arsenic-resistant patients reveal SUMO1-TOPORS and SUMO2/3-RNF4 degradation pathways.The Journal of cell biology · 2025Article
- Therapy-related myeloid neoplasms following curative treatment of acute promyelocytic leukemia: incidence, correlation with therapeutic regimen, and future directions.Journal of hematopathology · 2024Article
- Ablation of Wnt signaling in bone marrow stromal cells overcomes microenvironment-mediated drug resistance in acute myeloid leukemia.Scientific reports · 2024Article
- miR-603 promotes cell proliferation and differentiation by targeting TrkB in acute promyelocytic leukemia.Annals of hematology · 2023Article
- Metabolic adaptation drives arsenic trioxide resistance in acute promyelocytic leukemia.Blood advances · 2022Article
- Mutational profile of ZBTB16-RARA-positive acute myeloid leukemia.Cancer medicine · 2021Article
- Evolving Chemotherapy Free Regimens for Acute Promyelocytic Leukemia.Frontiers in oncology · 2021Review
- Management of relapse in acute promyelocytic leukaemia treated with up-front arsenic trioxide-based regimens.British journal of haematology · 2021Article
- Arsenic trioxide inhibits the growth of cancer stem cells derived from small cell lung cancer by downregulating stem cell-maintenance factors and inducing apoptosis via the Hedgehog signaling blockade.Translational lung cancer research · 2020Article
- Review
- Acute Promyelocytic Leukemia: Update on the Mechanisms of Leukemogenesis, Resistance and on Innovative Treatment Strategies.Cancers · 2019Review
- Stromal cells downregulate miR-23a-5p to activate protective autophagy in acute myeloid leukemia.Cell death & disease · 2019Article
- Autophagy: New Insights into Mechanisms of Action and Resistance of Treatment in Acute Promyelocytic leukemia.International journal of molecular sciences · 2019Review
- Functional Profiling Identifies Determinants of Arsenic Trioxide Cellular Toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- 2-Bromopalmitate targets retinoic acid receptor alpha and overcomes all-trans retinoic acid resistance of acute promyelocytic leukemia.Haematologica · 2019Article
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
Abstract
There is limited data on the clinical, cellular and molecular changes in relapsed acute promyeloytic leukemia (RAPL) in comparison with newly diagnosed cases (NAPL). We undertook a prospective study to compare NAPL and RAPL patients treated with arsenic trioxide (ATO) based regimens. 98 NAPL and 28 RAPL were enrolled in this study. RAPL patients had a significantly lower WBC count and higher platelet count at diagnosis. IC bleeds was significantly lower in RAPL cases (P=0.022). The ability of malignant promyelocytes to concentrate ATO intracellularly and their in-vitro IC50 to ATO was not significantly different between the two groups. Targeted NGS revealed PML B2 domain mutations in 4 (15.38%) of the RAPL subset and none were associated with secondary resistance to ATO. A microarray GEP revealed 1744 genes were 2 fold and above differentially expressed between the two groups. The most prominent differentially regulated pathways were cell adhesion (n=92), cell survival (n=50), immune regulation (n=74) and stem cell regulation (n=51). Consistent with the GEP data, immunophenotyping revealed significantly increased CD34 expression (P=0.001) in RAPL cases and there was in-vitro evidence of significant microenvironment mediated innate resistance (EM-DR) to ATO. Resistance and relapse following treatment with ATO is probably multi-factorial, mutations in PML B2 domain while seen only in RAPL may not be the major clinically relevant cause of subsequent relapses. In RAPL additional factors such as expansion of the leukemia initiating compartment along with EM-DR may contribute significantly to relapse following treatment with ATO based regimens.
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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.