ArticleBlood cancer discovery2023
ETV6 Deficiency Unlocks ERG-Dependent Microsatellite Enhancers to Drive Aberrant Gene Activation in B-Lymphoblastic Leukemia.
Article in Blood cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 23 citations in OpenAlex.
- The nascent transcriptome delineates the regulatory landscape in human health and disease.bioRxiv : the preprint server for biology · 2026Article
- Article
- Simulating cell-free chromatin using preclinical cancer models for liquid biopsy applications.iScience · 2025Article
- EZH2-driven immune evasion at disease presentation defines a targetable high-risk subset of acute leukemia exemplified by t(16;21) FUS::ERG AML.bioRxiv : the preprint server for biology · 2025Article
- Selective Enhancer Dependencies in MYC-Intact and MYC-Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma.Blood cancer discovery · 2025Article
- Native stem cell transcriptional circuits define cardinal features of high-risk leukemia.The Journal of experimental medicine · 2025Article
- H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia.HemaSphere · 2025Article
- Altered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13).Blood advances · 2024Article
- ETS Transcription Factors in Immune Cells and Immune-Related Diseases.International journal of molecular sciences · 2024Review
- Oncogenic Enhancers in Leukemia.Blood cancer discovery · 2024Review
- Identification of Gene Regulatory Networks in B-Cell Progenitor Differentiation and Leukemia.Genes · 2024Article
- Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia.Current opinion in genetics & development · 2024Review
- The Diverse Roles of ETV6 Alterations in B-Lymphoblastic Leukemia and Other Hematopoietic Cancers.Advances in experimental medicine and biology · 2024Review
- Epigenomic mapping reveals distinct B cell acute lymphoblastic leukemia chromatin architectures and regulators.Cell genomics · 2023Article
- Article
- MLL-AF4 cooperates with PAF1 and FACT to drive high-density enhancer interactions in leukemia.Nature communications · 2023Article
- ETS Fight Club on Microsatellite Enhancers.Blood cancer discovery · 2023Article
Corrections and comments
- Commented on by
Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Distal enhancers play critical roles in sustaining oncogenic gene-expression programs. We identify aberrant enhancer-like activation of GGAA tandem repeats as a characteristic feature of B-cell acute lymphoblastic leukemia (B-ALL) with genetic defects of the ETV6 transcriptional repressor, including ETV6-RUNX1+ and ETV6-null B-ALL. We show that GGAA repeat enhancers are direct activators of previously identified ETV6-RUNX1+/- like B-ALL "signature" genes, including the likely leukemogenic driver EPOR. When restored to ETV6-deficient B-ALL cells, ETV6 directly binds to GGAA repeat enhancers, represses their acetylation, downregulates adjacent genes, and inhibits B-ALL growth. In ETV6-deficient B-ALL cells, we find that the ETS transcription factor ERG directly binds to GGAA microsatellite enhancers and is required for sustained activation of repeat enhancer-activated genes. Together, our findings reveal an epigenetic gatekeeper function of the ETV6 tumor suppressor gene and establish microsatellite enhancers as a key mechanism underlying the unique gene-expression program of ETV6-RUNX1+/- like B-ALL. SIGNIFICANCE: We find a unifying mechanism underlying a leukemia subtype-defining gene-expression signature that relies on repetitive elements with poor conservation between humans and rodents. The ability of ETV6 to antagonize promiscuous, nonphysiologic ERG activity may shed light on other roles of these key regulators in hematolymphoid development and human disease. See related commentary by Mercher, p. 2. This article is highlighted in the In This Issue feature, p. 1.
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.