ArticleNature communications2016
Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics.
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Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 63 citations in OpenAlex.
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- Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome.Rheumatology (Oxford, England) · 2021Article
- Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF in a case of atypical B-cell chronic lymphocytic leukemia harboring a t(14;18)(q32;q21).Cold Spring Harbor molecular case studies · 2021Article
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Authors and funding
44 authors at 20 institutions in 7 countries.
Eloy F RoblesDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, Pamplona 31008, Spain.
Maria Mena-VarasDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, Pamplona 31008, Spain.
Laura BarrioDepartment of Immunology and Oncology, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid 28049, Spain.
Sara V Merino-CortesDepartment of Immunology and Oncology, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid 28049, Spain.
Péter BaloghDepartment of Immunology and Biotechnology, Szentágothai Research Center, University of Pécs, Pécs H-7624, Hungary.
Ming-Qing DuDivision of Molecular Histopathology, Department of Pathology, Cambridge University, Cambridge CB2 1QP, UK.
Takashi AkasakaMRC Toxicology Unit and Ernest and Helen Scott Haematological Research Institute, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK.
Anton ParkerDepartment of Haematology, Royal Bournemouth Hospital, Bournemouth BH7 7DW, UK.
Sergio RoaDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, Pamplona 31008, Spain.
Carlos PanizoDepartment of Hematology, Clinica Universidad de Navarra, IDISNA, Pamplona 31008, Spain.
Idoia Martin-GuerreroInstitute of Human Genetics, Christian-Albrechts-University Kiel &University Hospital Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany.
Reiner SiebertInstitute of Human Genetics, Christian-Albrechts-University Kiel &University Hospital Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany.
Victor SeguraBio-informatic Unit, Department of Genomics and Proteomics, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, Pamplona 31008, Spain.
Xabier AgirreDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, Pamplona 31008, Spain.
Laura Macri-PellizeriDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, Pamplona 31008, Spain.
Beatriz AldazDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, Pamplona 31008, Spain.
Amaia Vilas-ZornozaDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, Pamplona 31008, Spain.
Shaowei ZhangDivision of Molecular Histopathology, Department of Pathology, Cambridge University, Cambridge CB2 1QP, UK.
Sarah MoodyDivision of Molecular Histopathology, Department of Pathology, Cambridge University, Cambridge CB2 1QP, UK.
Maria Jose CalasanzDepartment of Genetics, School of Medicine, University of Navarra, IDISNA, Pamplona 31008, Spain.
Thomas TousseynCentre for Translation Cell and Tissue Research, KU Leuven, Leuven 3000, Belgium.
Cyril BroccardoDepartment of Pathology, Institut Universitaire du Cancer de Toulouse-Oncopole, Labex TOUCAN and CRCT INSERM U1037, Toulouse F-31053, France.
Pierre BroussetDepartment of Pathology, Institut Universitaire du Cancer de Toulouse-Oncopole, Labex TOUCAN and CRCT INSERM U1037, Toulouse F-31053, France.
Elena Campos-SanchezCentro de Biologia Molecular Severo Ochoa, CSIC/Universidad Autonoma, Madrid 28049, Spain.
Cesar CobaledaCentro de Biologia Molecular Severo Ochoa, CSIC/Universidad Autonoma, Madrid 28049, Spain.
Isidro Sanchez-GarciaExperimental Therapeutics and Translational Oncology Program, Institute of Molecular and Cellular Biology of Cancer, CSIC/University of Salamanca; and Institute of Biomedical Research of Salamanca (IBSAL), Salamanca 37007, Spain.
Jose Luis Fernandez-LunaMolecular Genetics Unit, University Hospital Marques de Valdecilla and IFIMAV, Santander 39011, Spain.
Ricardo Garcia-MuñozHematology Department, Hospital San Pedro, Logroño, 26006, La Rioja, Spain.
Esther PenaDepartment of Hematology, Complejo Hospitalario de Navarra, Servicio Navarro de Salud, IDISNA, Pamplona 31008, Spain.
Beatriz BellosilloDepartment of Pathology, Cancer Research Program, Institut Municipal d'Investigacions Mèdiques (IMIM), Hospital del Mar, Barcelona 08003, Spain.
Antonio SalarDepartment of Clinical Hematology, Cancer Research Program, Institut Municipal d'Investigacions Mèdiques (IMIM), Hospital del Mar, Barcelona 08003, Spain.
Maria Joao BaptistaDepartment of Hematology, ICO-Hospital Universitari Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona 08916, Spain.
Jesús Maria Hernandez-RivasDepartment of Hematology, IBSAL-University Hospital and IBMCC-CSIC, University of Salamanca, Salamanca 37007, Spain.
Marcos GonzalezDepartment of Hematology, IBSAL-University Hospital and IBMCC-CSIC, University of Salamanca, Salamanca 37007, Spain.
Maria Jose TerolDepartment of Hematology, Hospital Clinico, INCLIVA Biomedical Research Institute, University of Valencia, Valencia 46010, Spain.
Joan ClimentDepartment of Hematology, Hospital Clinico, INCLIVA Biomedical Research Institute, University of Valencia, Valencia 46010, Spain.
Antonio FerrandezDepartment of Pathology, Hospital Clinico, University of Valencia, Valencia 46010, Spain.
Xavier SagaertCentre for Translation Cell and Tissue Research, KU Leuven, Leuven 3000, Belgium.
Ari M MelnickDepartment of Medicine/Hematology-Oncology, Weill Cornell Medical College, New York, New York 10065, USA.
Felipe ProsperDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, Pamplona 31008, Spain.
David G OscierDepartment of Haematology, Royal Bournemouth Hospital, Bournemouth BH7 7DW, UK.
Yolanda R CarrascoDepartment of Immunology and Oncology, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid 28049, Spain.
Martin J S DyerMRC Toxicology Unit and Ernest and Helen Scott Haematological Research Institute, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK.
Jose A Martinez-ClimentDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, Pamplona 31008, Spain.
Universidad de Navarra · ESCentro Nacional de Biotecnología · ESUniversity of Cambridge · GBCentre de Recherche en Cancérologie de Toulouse · FRCentro de Biología Molecular Severo Ochoa · ESClinica Universidad de Navarra · ESInstituto de Investigación Biomédica de Salamanca · ESKU Leuven · BERoyal Bournemouth Hospital · GBUniversity Hospital Schleswig-Holstein · DECornell University · USHospital Clínico Universitario de Valencia · ESHospital del Mar Research Institute · ESHospital San Pedro · ESINCLIVA Health Research Institute · ESJosep Carreras Leukaemia Research Institute · ESMarqués de Valdecilla University Hospital · ESMRC Toxicology Unit · GBMunicipal Institute for Medical Research · ESServicio Navarro de Salud · ES
Funding
Worldwide Cancer Research 15-1322
Abstract
NKX2 homeobox family proteins have a role in cancer development. Here we show that NKX2-3 is overexpressed in tumour cells from a subset of patients with marginal-zone lymphomas, but not with other B-cell malignancies. While Nkx2-3-deficient mice exhibit the absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells show marginal-zone expansion that leads to the development of tumours, faithfully recapitulating the principal clinical and biological features of human marginal-zone lymphomas. NKX2-3 induces B-cell receptor signalling by phosphorylating Lyn/Syk kinases, which in turn activate multiple integrins (LFA-1, VLA-4), adhesion molecules (ICAM-1, MadCAM-1) and the chemokine receptor CXCR4. These molecules enhance migration, polarization and homing of B cells to splenic and extranodal tissues, eventually driving malignant transformation through triggering NF-κB and PI3K-AKT pathways. This study implicates oncogenic NKX2-3 in lymphomagenesis, and provides a valid experimental mouse model for studying the biology and therapy of human marginal-zone B-cell lymphomas.
Indexed as
AnimalsCell Adhesion MoleculesGene Expression ProfilingHomeodomain ProteinsHumansKaplan-Meier EstimateLymphocytesLymphoid TissueLymphoma, B-Cell, Marginal ZoneMice, Inbred C57BLMice, KnockoutPhosphorylationReceptors, Antigen, B-CellSignal TransductionSyk KinaseTranscription FactorsCell Adhesion MoleculesHomeodomain ProteinsNKX2-3 protein, humanNkx2.3 protein, mouseReceptors, Antigen, B-CellSyk KinaseTranscription Factors
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