ArticleBlood cancer discovery2021
Hyperthermia Selectively Destabilizes Oncogenic Fusion Proteins.
Article in Blood cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.
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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.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Arsenic trioxide could promote SARS-CoV-2 NSP12 protein degradation.The Journal of general virology · 2025Article
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- Temperature induces brain-intake shift of recombinant high-density lipoprotein after traumatic brain injury.Journal of nanobiotechnology · 2024Article
- A case report of acute promyelocytic leukemia with myeloid sarcoma of the lumbar spine and literature review.Frontiers in medicine · 2024Review
- Hyperthermia promotes degradation of the acute promyelocytic leukemia driver oncoprotein ZBTB16/RARα.Acta pharmacologica Sinica · 2023Article
- The genomic landscape of sensitivity to arsenic trioxide uncovered by genome-wide CRISPR-Cas9 screening.Frontiers in oncology · 2023Article
- The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions.Bioengineering (Basel, Switzerland) · 2022Review
- Sacubitril/valsartan protects against arsenic trioxide induced cardiotoxicity in vivo and in vitro.Toxicology research · 2022Article
- PRMT5-mediated RNF4 methylation promotes therapeutic resistance of APL cells to AsCellular and molecular life sciences : CMLS · 2022Article
- Magnetite Nanoparticles in Magnetic Hyperthermia and Cancer Therapies: Challenges and Perspectives.Nanomaterials (Basel, Switzerland) · 2022Review
- Linear and Circular Long Non-Coding RNAs in Acute Lymphoblastic Leukemia: From Pathogenesis to Classification and Treatment.International journal of molecular sciences · 2022Review
- Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load.Research (Washington, D.C.) · 2022Article
- Hyperthermia combined with immune checkpoint inhibitor therapy in the treatment of primary and metastatic tumors.Frontiers in immunology · 2022Review
- Arsenic Trioxide Therapy During Pregnancy: ATO and Its Metabolites in Maternal Blood and Amniotic Fluid of Acute Promyelocytic Leukemia Patients.Frontiers in oncology · 2022Article
- Article
- Recent Advancements in Hyperthermia-Driven Controlled Drug Delivery from Nanotherapeutics.Recent advances in drug delivery and formulation · 2022Article
- PML/RARA destabilization by hyperthermia: a new model for oncogenic fusion protein degradation?Blood cancer discovery · 2021Article
- Modulation of Phase Separation by RNA: A Glimpse on NFrontiers in cell and developmental biology · 2021Review
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Authors and funding
39 authors at 18 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to drug-resistant mutations. Here we report that thermal stress destabilizes the PML/RARα protein, including clinically identified drug-resistant mutants. AML1/ETO and TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of PML/RARα in complex with nuclear receptor corepressors leading to ubiquitin-mediated degradation via the SIAH2 E3 ligase. Hyperthermia and arsenic therapy destabilize PML/RARα via distinct mechanisms and are synergistic in primary patient samples and SIGNIFICANCE: Hyperthermia destabilizes oncofusion proteins including PML/RARα and acts synergistically with standard arsenic therapy in relapsed and refractory APL. The results open up the possibility that heat shock sensitivity may be an easily targetable vulnerability of oncofusion-driven cancers.
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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.