ArticleCancer cell2015
Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia.
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Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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78citing papers in PubMed
13.9field-weighted citation impact, top 1% of its field
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Who cites it
78 citing papers in PubMed, 133 citations in OpenAlex.
- Author Correction: Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia.Nature · 2026Article
- BCR::ABL1-Induced Enhancer Reprogramming Uncovers Hypersensitivity of Ph+B-ALL Cells to Enhancer-Targeting Drugs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Variable thresholds for phosphorylation targets of the ERK signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Common origins of autoimmune diseases and lymphoid malignancies.Trends in immunology · 2025Review
- The Inositol-5-Phosphatase SHIP1: Expression, Regulation and Role in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- ASCL1 Restrains ERK1/2 to Promote Survival of a Subset of Neuroendocrine Lung Cancers.Molecular cancer therapeutics · 2024Article
- Ikaros sets the threshold for negative B-cell selection by regulation of the signaling strength of the AKT pathway.Cell communication and signaling : CCS · 2024Article
- DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer.EMBO molecular medicine · 2024Article
- Concepts in B cell acute lymphoblastic leukemia pathogenesis.Journal of leukocyte biology · 2024Review
- Article
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- XBP1 promotes NRASJournal of cellular and molecular medicine · 2023Article
- SPRY4-dependent ERK negative feedback demarcates functional adult stem cells in the male mouse germline†.Biology of reproduction · 2023Article
- Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer.Cell cycle (Georgetown, Tex.) · 2023Article
- In Vitro and In Silico Investigation of BCI Anticancer Properties and Its Potential for Chemotherapy-Combined Treatments.Cancers · 2023Article
- The ERK activator, BCI, inhibits ciliogenesis and causes defects in motor behavior, ciliary gating, and cytoskeletal rearrangement.Life science alliance · 2023Article
- TFEB inhibition induces melanoma shut-down by blocking the cell cycle and rewiring metabolism.Cell death & disease · 2023Article
- Decrypting drug actions and protein modifications by dose- and time-resolved proteomics.Science (New York, N.Y.) · 2023Article
- Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?Annual review of pharmacology and toxicology · 2023Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 10 institutions in 4 countries.
Seyedmehdi ShojaeeDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Rebecca CaeserDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA; Department of Haematology, University of Cambridge, Cambridge CB2 0AH, UK.
Maike BuchnerDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Eugene ParkDepartment of Haematology, University of Cambridge, Cambridge CB2 0AH, UK.
Srividya SwaminathanDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Christian HurtzDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Huimin GengDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Lai N ChanDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Lars KlemmDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Wolf-Karsten HofmannIII. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Heidelberg 68167, Germany.
Yi Hua QiuDepartment of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Nianxiang ZhangDepartment of Bioinformatics and Computational Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Kevin R CoombesDepartment of Bioinformatics and Computational Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Elisabeth PaiettaAlbert Einstein College of Medicine, Bronx, NY 10466, USA.
Jeffery MolkentinHoward Hughes Medical Institute and Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH 45247, USA.
H Phillip KoefflerDivision of Hematology and Oncology, Cedars Sinai Medical Center, Los Angeles, CA 90095, USA; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
Cheryl L WillmanDepartment of Pathology, University of New Mexico Cancer Center, Albuquerque, NM 87102, USA.
Stephen P HungerDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Ari MelnickDepartments of Medicine and Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA.
Steven M KornblauDepartment of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Markus MüschenDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address: markus.muschen@ucsf.edu.
University of California, San Francisco · USThe University of Texas MD Anderson Cancer Center · USAlbert Einstein College of Medicine · USCedars-Sinai Medical Center · USChildren's Hospital of Philadelphia · USCincinnati Children's Hospital Medical Center · USCornell University · USHeidelberg University · DEUniversity of Cambridge · GBUniversity of New Mexico · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MProject-006U10CA180820 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer, MITCHELL D. SCHNALL · 2014 to 2026
$167.6MECOG OPERATIONS OFFICE (IBCSG)U10CA021115 · NCI · UNIVERSITY OF WISCONSIN MADISON · PI COMIS, ROBERT L · 1985 to 2013
$132.6MStatistics CoreU10CA180794 · NCI · DANA-FARBER CANCER INST · PI PAUL J CATALANO, CONSTANTINE A. GATSONIS · 2014 to 2026
$111.2MECOG-ACRIN Biospecimen Bank to Support NCTNU24CA196172 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI STANLEY R. HAMILTON, Scott D Jewell · 2015 to 2026
$41.1MMontefiore Academic Community NCORP ProgramUG1CA189859 · NCI · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI Balazs Halmos, Della Makower · 2014 to 2026
$10.8MTargeted activation of autoimmune checkpoints in B cell malignanciesR01CA157644 · NCI · YALE UNIVERSITY · PI Markus Müschen · 2011 to 2026
$5.7MECOG-ACRIN INTEGRATED LEUKEMIA TRANSLATIONAL RESEARCH CENTERU10CA180827 · NCI · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI LEVINE, ROSS L, MELNICK, ARI M. · 2014 to 2018
$3.0MPRE-B CELL RECEPTOR SIGNALING IN ACUTE LYMPHOBLASTIC LEUKEMIAR01CA137060 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MÜSCHEN, MARKUS · 2009 to 2016
$2.7MAID-mediated genetic instability in BCR-ABL1-transformed B cell lineage leukemiaR01CA139032 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MÜSCHEN, MARKUS · 2009 to 2013
$1.6MNegative feedback signaling in tyrosine kinase-driven leukemiaR01CA172558 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MÜSCHEN, MARKUS · 2013 to 2015
$972kTargeting BCL6 in tyrosine kinase-driven leukemiaR01CA169458 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MÜSCHEN, MARKUS · 2013 to 2015
$972kCancer Research UK 18131NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA137060NCI NIH HHS R01 CA139032NCI NIH HHS R01 CA157644NCI NIH HHS R01 CA169458NCI NIH HHS R01 CA172558NCI NIH HHS U10 CA021115NCI NIH HHS U10 CA180794NCI NIH HHS U10 CA180820NCI NIH HHS U10 CA180827NCI NIH HHS U24 CA196172NCI NIH HHS UG1 CA189859Wellcome Trust 101880
Abstract
Studying mechanisms of malignant transformation of human pre-B cells, we found that acute activation of oncogenes induced immediate cell death in the vast majority of cells. Few surviving pre-B cell clones had acquired permissiveness to oncogenic signaling by strong activation of negative feedback regulation of Erk signaling. Studying negative feedback regulation of Erk in genetic experiments at three different levels, we found that Spry2, Dusp6, and Etv5 were essential for oncogenic transformation in mouse models for pre-B acute lymphoblastic leukemia (ALL). Interestingly, a small molecule inhibitor of DUSP6 selectively induced cell death in patient-derived pre-B ALL cells and overcame conventional mechanisms of drug-resistance.
Indexed as
MAP Kinase Signaling SystemAnimalsAntineoplastic AgentsCell Transformation, NeoplasticDNA-Binding ProteinsDual Specificity Phosphatase 6Host Cell Factor C1HumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceMice, TransgenicMolecular Sequence DataPrecursor Cell Lymphoblastic Leukemia-LymphomaPrognosisProtein Serine-Threonine KinasesAntineoplastic AgentsDNA-Binding ProteinsDual Specificity Phosphatase 6Dusp6 protein, mouseEtv5 protein, mouseHost Cell Factor C1Intracellular Signaling Peptides and ProteinsMembrane ProteinsProtein Serine-Threonine KinasesSmall Molecule LibrariesSpry2 protein, mouseTranscription Factors
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