ArticleBlood2012
BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers, 2 of them syntheses that pooled it.
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
235 citing papers in PubMed, 2 syntheses or guidelines pooled it, 368 citations in OpenAlex.
- The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review.Journal of applied biomedicine · 2024Pooled it
- A loss of function screen of identified genome-wide association study Loci reveals new genes controlling hematopoiesis.PLoS genetics · 2014Pooled it
- Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.Molecules (Basel, Switzerland) · 2026Review
- (+)-JQ1 Upregulates SIRT3 to Suppress cGAS/STING Pathway-Mediated Neuronal Inflammation and Ferroptosis After Hypoxic-Ischemic Encephalopathy.Drug design, development and therapy · 2026Article
- Preclinical efficacy of tasquinimod-based combinations in advanced myeloproliferative neoplasms in blastic phase.Blood advances · 2025Article
- Pan-cancer Myc modulator that targets Myc-α-tubulin interaction to drive selective mitotic catastrophe.Scientific reports · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Targeting CLEC4E in immunosuppressive tumour-associated macrophages via BET inhibition.Clinical and translational medicine · 2025Article
- Age-Driven Genetic and Epigenetic Heterogeneity in B-ALL.International journal of molecular sciences · 2025Review
- Immunotherapy resistance in non-small cell lung cancer: from mechanisms to therapeutic opportunities.Journal of experimental & clinical cancer research : CR · 2025Review
- A circular RNA overcomes acquired resistance to BET inhibitors by antagonizing IGF2BP2-mediated c-MYC translation in TNBC.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Promising Drugs Targeting Specific Mechanisms of Deregulation in T Cell Lineage Acute Lymphoblastic Leukemia.Oncology and therapy · 2025Review
- Recommended Tool Compounds: Thienotriazolodiazepines-Derivatized Chemical Probes to Target BET Bromodomains.ACS pharmacology & translational science · 2025Review
- Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure.HemaSphere · 2025Article
- Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction.Cell communication and signaling : CCS · 2024Article
- The Killer's Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer.International journal of molecular sciences · 2024Review
- Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction.bioRxiv : the preprint server for biology · 2023Article
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- BRD4 Inhibition Enhances the Antitumor Effects of Radiation Therapy in a Murine Breast Cancer Model.International journal of molecular sciences · 2023Article
- A Novel Acetylation-Immune Subtyping for the Identification of a BET Inhibitor-Sensitive Subgroup in Melanoma.Pharmaceuticals (Basel, Switzerland) · 2023Article
175 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
We investigated the therapeutic potential of JQ1, an inhibitor of the BET class of human bromodomain proteins, in B-cell acute lymphoblastic leukemia (B-ALL). We show that JQ1 potently reduces the viability of B-ALL cell lines with high-risk cytogenetics. Among the most sensitive were lines with rearrangements of CRLF2, which is overexpressed in ~ 10% of B-ALL. CRLF2 heterodimerizes with the IL7 receptor (IL7R) and signals through JAK2, JAK1, and STAT5 to drive proliferation and suppress apoptosis. As previously observed, JQ1 induced the down-regulation of MYC transcription, the loss of BRD4 at the MYC promoter, and the reduced expression of c-Myc target genes. Strikingly, JQ1 also down-regulated IL7R transcription, depleted BRD4 from the IL7R promoter, and reduced JAK2 and STAT5 phosphorylation. Genome-wide expression profiling demonstrated a restricted effect of JQ1 on transcription, with MYC and IL7R being among the most down-regulated genes. Indeed, IL7R was the only cytokine receptor in CRLF2-rearranged B-ALL cells significantly down-regulated by JQ1 treatment. In mice xenografted with primary human CRLF2-rearranged B-ALL, JQ1 suppressed c-Myc expression and STAT5 phosphorylation and significantly prolonged survival. Thus, bromodomain inhibition is a promising therapeutic strategy for B-ALL as well as other conditions dependent on IL7R signaling.
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.