ArticleNature immunology2017
Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival.
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Article in Nature immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 88 citations in OpenAlex.
- Pathway incompatibility between NF-κB and RAS signaling constrains oncogenicity in B-cell leukemia.The Journal of biological chemistry · 2026Article
- IKAROS isoforms differentially control gene expression and differentiation of a B-cell acute lymphoblastic leukemia cell line.Nagoya journal of medical science · 2026Article
- BCR::ABL1-Induced Enhancer Reprogramming Uncovers Hypersensitivity of Ph+B-ALL Cells to Enhancer-Targeting Drugs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dynamic feedback control of oncogenic tyrosine kinase signaling in acute leukemia.Science signaling · 2026Article
- IKAROS Gene Regulatory Network Reveal ERG as a Vulnerability in B-cell Acute Lymphoblastic Leukemia.bioRxiv : the preprint server for biology · 2025Article
- Aiolos restricts the generation of antigen-inexperienced, virtual memory CD8Nature communications · 2025Article
- The Crosstalk Between B Cells and the Skeletal System During Development, Aging, and in Pathological Conditions.Current osteoporosis reports · 2025Review
- Models for T-large granular lymphocytic leukemia: how to mimic the cellular interplays in malignant autoimmunity.Leukemia · 2025Review
- Super enhancers as key drivers of gene regulatory networks in normal and malignant hematopoiesis.Frontiers in cell and developmental biology · 2025Review
- Identification of hub genes in congenital hypothyroidism and construction of the associated immune regulatory network.Frontiers in immunology · 2025Article
- Secondary lesions and sensitivity to signaling inhibitors in iAMP21 acute lymphoblastic leukemia.HemaSphere · 2025Article
- Lipopolymer/siRNA Nanoparticles Targeting the Signal Transducer and Activator of Transcription 5A Disrupts Proliferation of Acute Lymphoblastic Leukemia.ACS pharmacology & translational science · 2024Article
- Article
- Stat5 induces androgen receptor (Science advances · 2024Article
- Stem cell-like reprogramming is required for leukemia-initiating activity in B-ALL.The Journal of experimental medicine · 2024Article
- The transcription factor Aiolos restrains the activation of intestinal intraepithelial lymphocytes.Nature immunology · 2024Article
- IKAROS Family Transcription Factors in Lymphocyte Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Ikaros is a principal regulator of AireScience immunology · 2023Article
- Defining the Basal and Immunomodulatory Mediator-Induced Phosphoprotein Signature in Pediatric B Cell Acute Lymphoblastic Leukemia (B-ALL) Diagnostic Samples.International journal of molecular sciences · 2023Article
- Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors.Scientific reports · 2023Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 10 institutions in 2 countries.
Casey D S KaterndahlDepartment of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Lynn M Heltemes-HarrisDepartment of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Mark J L WilletteDepartment of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Christine M HenzlerSupercomputing Institute for Advanced Computational Research, University of Minnesota, Minneapolis, Minnesota, USA.
Seth FrietzeMLRS Department, University of Vermont, Burlington, Vermont, USA.
Rendong YangSupercomputing Institute for Advanced Computational Research, University of Minnesota, Minneapolis, Minnesota, USA.
Hilde SchjervenDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0001-9287-3375
Kevin A T SilversteinSupercomputing Institute for Advanced Computational Research, University of Minnesota, Minneapolis, Minnesota, USA.
Laura B RamseyDepartment of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Gregory HubbardDepartment of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Andrew D WellsDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Roland P KuiperPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Blanca ScheijenLaboratory of Pediatric Oncology Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
Frank N van LeeuwenLaboratory of Pediatric Oncology Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
Markus MüschenDepartment of Systems Biology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Pasadena, California, USA.
Steven M KornblauDepartment of Leukemia, The University of Texas Maryland Anderson Cancer Center, Houston, Texas, USA.
Michael A FarrarDepartment of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-5569-0366
University of Minnesota Medical Center · USUniversity of Minnesota · USRadboud University Nijmegen · NLChildren's Hospital of Philadelphia · USCincinnati Children's Hospital Medical Center · USCity of Hope · USPrincess Máxima Center · NLThe University of Texas MD Anderson Cancer Center · USUniversity of California, San Francisco · USUniversity of Vermont · US
Funding
Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4MUniversity of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y · 2003 to 2023
$43.7MMetabolic gatekeepers in B-cell malignanciesR35CA197628 · NCI · YALE UNIVERSITY · PI Markus Müschen · 2016 to 2026
$11.7MIMMUNOLOGY TRAINING PROGRAMT32AI007313 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Carla Rothlin · 1989 to 2026
$5.7MTargeted activation of autoimmune checkpoints in B cell malignanciesR01CA157644 · NCI · YALE UNIVERSITY · PI Markus Müschen · 2011 to 2026
$5.7MPRE-B CELL RECEPTOR SIGNALING IN ACUTE LYMPHOBLASTIC LEUKEMIAR01CA137060 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MÜSCHEN, MARKUS · 2009 to 2016
$2.7MCD25-mediated feedback control of BCR-signaling and its oncogenic mimicsR01CA213138 · NCI · YALE UNIVERSITY · PI MÜSCHEN, MARKUS · 2017 to 2022
$1.9MAID-mediated genetic instability in BCR-ABL1-transformed B cell lineage leukemiaR01CA139032 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MÜSCHEN, MARKUS · 2009 to 2013
$1.6MPre-BCR and STAT5 Signaling in Acute Lymphoblastic LeukemiaR01CA151845 · NCI · UNIVERSITY OF MINNESOTA · PI FARRAR, MICHAEL ARCHIBALD · 2011 to 2015
$1.5MTransponson-based screens for genes involved in acute lymphoblastic LeukemiaR01CA154998 · NCI · UNIVERSITY OF MINNESOTA · PI FARRAR, MICHAEL ARCHIBALD · 2011 to 2015
$1.5M(PQB3) CD4 T cell response to BCR-ABL-positive LeukemiaR01CA185062 · NCI · UNIVERSITY OF MINNESOTA · PI FARRAR, MICHAEL ARCHIBALD · 2014 to 2017
$1.2MNegative feedback signaling in tyrosine kinase-driven leukemiaR01CA172558 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MÜSCHEN, MARKUS · 2013 to 2015
$972kNCI NIH HHS P30 CA077598NCI NIH HHS P50 CA100632NCI NIH HHS R01 CA137060NCI NIH HHS R01 CA139032NCI NIH HHS R01 CA151845NCI NIH HHS R01 CA154998NCI NIH HHS R01 CA157644NCI NIH HHS R01 CA169458NCI NIH HHS R01 CA172558NCI NIH HHS R01 CA185062NCI NIH HHS R01 CA213138NCI NIH HHS R21 CA209229NCI NIH HHS R35 CA197628NIAID NIH HHS T32 AI007313
Abstract
The transcription factor STAT5 has a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we found that activation of STAT5 worked together with defects in signaling components of the precursor to the B cell antigen receptor (pre-BCR), including defects in BLNK, BTK, PKCβ, NF-κB1 and IKAROS, to initiate B-ALL. STAT5 antagonized the transcription factors NF-κB and IKAROS by opposing regulation of shared target genes. Super-enhancers showed enrichment for STAT5 binding and were associated with an opposing network of transcription factors, including PAX5, EBF1, PU.1, IRF4 and IKAROS. Patients with a high ratio of active STAT5 to NF-κB or IKAROS had more-aggressive disease. Our studies indicate that an imbalance of two opposing transcriptional programs drives B-ALL and suggest that restoring the balance of these pathways might inhibit B-ALL.
Indexed as
B-LymphocytesGene Expression Regulation, NeoplasticAdaptor Proteins, Signal TransducingAgammaglobulinaemia Tyrosine KinaseAnimalsChromatin ImmunoprecipitationFlow CytometryHumansIkaros Transcription FactorInterferon Regulatory Factor-4Interferon Regulatory FactorsMiceMultiplex Polymerase Chain ReactionNF-kappa B p50 SubunitPAX5 Transcription FactorPre-B Cell ReceptorsAdaptor Proteins, Signal TransducingAgammaglobulinaemia Tyrosine KinaseB cell linker proteinBTK protein, humanEbf1 protein, mouseIkaros Transcription FactorIKZF1 protein, humanInterferon Regulatory Factor-4Interferon Regulatory FactorsNF-kappa B p50 SubunitNfkb1 protein, mousePax5 protein, mousePAX5 Transcription FactorPre-B Cell ReceptorsPrkcb protein, mouseProtein Kinase C betaProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Protein Spi-1STAT5 Transcription FactorTrans-ActivatorsZfpn1a1 protein, mouse
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