ArticleMolecular cancer therapeutics2014
Targeting STAT5 in hematologic malignancies through inhibition of the bromodomain and extra-terminal (BET) bromodomain protein BRD2.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 62 citations in OpenAlex.
- Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets.Frontiers in immunology · 2025Review
- Identification of Plasma Protein Biomarkers and Drug Targets for Hematologic Malignancies by Proteome-wide Mendelian Randomization.Journal of Cancer · 2025Article
- Recent research on the association between signal transducer and activator of transcription 5 and childhood acute lymphoblastic leukemia.Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022Review
- Chemogenomics for drug discovery: clinical molecules from open access chemical probes.RSC chemical biology · 2021Review
- Selective BET-bromodomain inhibition by JQ1 suppresses dendritic cell maturation and antigen-specific T-cell responses.Cancer immunology, immunotherapy : CII · 2021Article
- B-ALL Complexity: Is Targeted Therapy Still A Valuable Approach for Pediatric Patients?Cancers · 2020Review
- Acute Systemic Inflammatory Response Alters Transcription Profile of Genes Related to Immune Response and CaInternational journal of molecular sciences · 2020Article
- Involvement of STAT5 in Oncogenesis.Biomedicines · 2020Review
- BET proteins: Investigating BRDT as a potential target for male contraception.Bioorganic & medicinal chemistry letters · 2020Review
- Bromodomain and Extraterminal Inhibition by JQ1 Produces Divergent Transcriptional Regulation of Suppressors of Cytokine Signaling Genes in Adipocytes.Endocrinology · 2020Article
- Epigenetic Control of a Local Chromatin Landscape.International journal of molecular sciences · 2020Review
- Pharmacological Inhibition of Oncogenic STAT3 and STAT5 Signaling in Hematopoietic Cancers.Cancers · 2020Review
- Review
- Risk stratification for lung adenocarcinoma on EGFR and TP53 mutation status, chemotherapy, and PD-L1 immunotherapy.Cancer medicine · 2019Article
- Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy.Cancers · 2019Review
- Bromodomain and extra-terminal motif inhibitors: a review of preclinical and clinical advances in cancer therapy.Future science OA · 2019Review
- The transcription factor STAT5 catalyzes Mannich ligation reactions yielding inhibitors of leukemic cell proliferation.Nature communications · 2019Article
- The epigenome in pediatric acute lymphoblastic leukemia: drug resistance and therapeutic opportunities.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- STAT5 inhibition induces TRAIL/DR4 dependent apoptosis in peripheral T-cell lymphoma.Oncotarget · 2018Article
- Exploiting a water network to achieve enthalpy-driven, bromodomain-selective BET inhibitors.Bioorganic & medicinal chemistry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The transcription factor signal STAT5 is constitutively activated in a wide range of leukemias and lymphomas, and drives the expression of genes necessary for proliferation, survival, and self-renewal. Thus, targeting STAT5 is an appealing therapeutic strategy for hematologic malignancies. Given the importance of bromodomain-containing proteins in transcriptional regulation, we considered the hypothesis that a pharmacologic bromodomain inhibitor could inhibit STAT5-dependent gene expression. We found that the small-molecule bromodomain and extra-terminal (BET) bromodomain inhibitor JQ1 decreases STAT5-dependent (but not STAT3-dependent) transcription of both heterologous reporter genes and endogenous STAT5 target genes. JQ1 reduces STAT5 function in leukemia and lymphoma cells with constitutive STAT5 activation, or inducibly activated by cytokine stimulation. Among the BET bromodomain subfamily of proteins, it seems that BRD2 is the critical mediator for STAT5 activity. In experimental models of acute T-cell lymphoblastic leukemias, where activated STAT5 contributes to leukemia cell survival, Brd2 knockdown or JQ1 treatment shows strong synergy with tyrosine kinase inhibitors (TKI) in inducing apoptosis in leukemia cells. In contrast, mononuclear cells isolated form umbilical cord blood, which is enriched in normal hematopoietic precursor cells, were unaffected by these combinations. These findings indicate a unique functional association between BRD2 and STAT5, and suggest that combinations of JQ1 and TKIs may be an important rational strategy for treating leukemias and lymphomas driven by constitutive STAT5 activation.
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.