ArticleCancer discovery2023
Structural Basis of PML-RARA Oncoprotein Targeting by Arsenic Unravels a Cysteine Rheostat Controlling PML Body Assembly and Function.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Discovery of novel murine PML isoforms.Nucleus (Austin, Tex.) · 2026Article
- Rethinking Drug Resistance in Acute Promyelocytic Leukemia: The Regulated Cell Death Network as an Integrative Framework.Biomolecules · 2026Review
- Deficient arsenic methylation and global proteomic reprogramming in human keratinocytes during arsenic-induced skin carcinogenesis.Archives of toxicology · 2026Article
- The promyelocytic leukemia PML protein coordinates immune evasion in triple-negative breast cancer via independent and converging mechanisms.Cell death and differentiation · 2026Article
- Bortezomib synergizes with homoharringtonine in FLT3-ITD-relapsed/refractory acute myeloid leukemia by inducing FLT3-ITD protein degradation.Clinical and experimental medicine · 2026Article
- Venetoclax induces mitochondrial apoptosis and autophagy to overcome arsenic trioxide resistance in acute promyelocytic leukemia.Journal of translational medicine · 2026Article
- The Extrachromosomal DNA Fusion Factory: Extrachromosomal Genesis of Oncogenic Fusion Transcripts.Research (Washington, D.C.) · 2026Article
- Atypical acute promyelocytic leukemia with tripartite fusion geneHaematologica · 2025Article
- Disease-specific epigenetic deregulation of enhancers, transposons, and polycomb targets in acute promyelocytic leukemia.Genome medicine · 2025Article
- ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions.Molecular biomedicine · 2025Review
- Drug Repurposing for AML: Structure-Based Virtual Screening and Molecular Simulations of FDA-Approved Compounds with Polypharmacological Potential.Biomedicines · 2025Article
- Identification of a novel PML exon 6 splice variant in atypical PML::RARα transcripts in acute promyelocytic leukemia.Annals of hematology · 2025Article
- Patients with high-risk acute promyelocytic leukemia need maintenance therapy for 1 year - the CONS.Haematologica · 2025Article
- Biomolecular condensates in immune cell fate.Nature reviews. Immunology · 2025Review
- ALLG APML5: bioavailability and safety of oral arsenic trioxide assessed during consolidation therapy for APL.Blood advances · 2025Article
- Conventional chemotherapy: millions of cures, unresolved therapeutic index.Nature reviews. Cancer · 2025Review
- Infection-related pathway activation and vulnerability to arsenic trioxide in acute promyelocytic leukemia with TTMV::RARA.Leukemia · 2025Article
- Mutation in the UnrearrangedResearch (Washington, D.C.) · 2025Article
- Synthesis and structural characterization of the heavy tricysteinylpnictines, models of protein-bound As(III), Sb(III), and Bi(III).Dalton transactions (Cambridge, England : 2003) · 2024Article
- PML Nuclear bodies: the cancer connection and beyond.Nucleus (Austin, Tex.) · 2024Review
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21 authors at 5 institutions in 4 countries.
Funding
Abstract
PML nuclear bodies (NB) are disrupted in PML-RARA-driven acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) cures 70% of patients with APL, driving PML-RARA degradation and NB reformation. In non-APL cells, arsenic binding onto PML also amplifies NB formation. Yet, the actual molecular mechanism(s) involved remain(s) elusive. Here, we establish that PML NBs display some features of liquid-liquid phase separation and that ATO induces a gel-like transition. PML B-box-2 structure reveals an alpha helix driving B2 trimerization and positioning a cysteine trio to form an ideal arsenic-binding pocket. Altering either of the latter impedes ATO-driven NB assembly, PML sumoylation, and PML-RARA degradation, mechanistically explaining clinical ATO resistance. This B2 trimer and the C213 trio create an oxidation-sensitive rheostat that controls PML NB assembly dynamics and downstream signaling in both basal state and during stress response. These findings identify the structural basis for arsenic targeting of PML that could pave the way to novel cancer drugs. SIGNIFICANCE: Arsenic curative effects in APL rely on PML targeting. We report a PML B-box-2 structure that drives trimer assembly, positioning a cysteine trio to form an arsenic-binding pocket, which is disrupted in resistant patients. Identification of this ROS-sensitive triad controlling PML dynamics and functions could yield novel drugs. See related commentary by Salomoni, p. 2505. This article is featured in Selected Articles from This Issue, p. 2489.
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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.