ArticleBlood2022
Noncanonical EZH2 drives retinoic acid resistance of variant acute promyelocytic leukemias.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Epigenetic reprogramming of lineage switching in cancer.FEBS letters · 2026Review
- Integrated Proteomic and Metabolomic Profiling in Acute Promyelocytic Leukemia: Current Status and Perspectives.International journal of general medicine · 2025Review
- Review
- Predictive modelling of acute Promyelocytic leukaemia resistance to retinoic acid therapy.Briefings in bioinformatics · 2024Article
- Retinoids and EZH2 inhibitors cooperate to orchestrate anti-oncogenic effects on bladder cancer cells.Cancer gene therapy · 2024Article
- Function of PML-RARA in Acute Promyelocytic Leukemia.Advances in experimental medicine and biology · 2024Review
- Non-canonical functions of EZH2 in cancer.Frontiers in oncology · 2023Review
- Dual inhibition of EZH2 and G9A/GLP histone methyltransferases by HKMTI-1-005 promotes differentiation of acute myeloid leukemia cells.Frontiers in cell and developmental biology · 2023Article
- Single Cell Transcriptomics to Understand HSC Heterogeneity and Its Evolution upon Aging.Cells · 2022Review
- An Acute Promyelocytic Leukemia Resistant to All-Trans Retinoic Acid: A Case Report of theCase reports in oncologyArticle
Corrections and comments
- Commented on by
Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cell heterogeneity is a major driver of therapy resistance. To characterize resistant cells and their vulnerabilities, we studied the PLZF-RARA variant of acute promyelocytic leukemia, resistant to retinoic acid (RA), using single-cell multiomics. We uncovered transcriptional and chromatin heterogeneity in leukemia cells. We identified a subset of cells resistant to RA with proliferation, DNA replication, and repair signatures that depend on a fine-tuned E2F transcriptional network targeting the epigenetic regulator enhancer of zeste homolog 2 (EZH2). Epigenomic and functional analyses validated the driver role of EZH2 in RA resistance. Targeting pan-EZH2 activities (canonical/noncanonical) was necessary to eliminate leukemia relapse-initiating cells, which underlies a dependency of resistant cells on an EZH2 noncanonical activity and the necessity to degrade EZH2 to overcome resistance. Our study provides critical insights into the mechanisms of RA resistance that allow us to eliminate treatment-resistant leukemia cells by targeting EZH2, thus highlighting a potential targeted therapy approach. Beyond RA resistance and acute promyelocytic leukemia context, our study also demonstrates the power of single-cell multiomics to identify, characterize, and clear therapy-resistant cells.
Indexed as
Identifiers
What OpenQuestion holds
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.