Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-03-29

AUTHORS

S Geyh, S Öz, R-P Cadeddu, J Fröbel, B Brückner, A Kündgen, R Fenk, I Bruns, C Zilkens, D Hermsen, N Gattermann, G Kobbe, U Germing, F Lyko, R Haas, T Schroeder

ABSTRACT

Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS–MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS–MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS. More... »

PAGES

1841-1851

References to SciGraph publications

  • 2010-08. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche in NATURE
  • 2013-01-22. Tracking of Replicative Senescence in Mesenchymal Stem Cells by Colony-Forming Unit Frequency in STEM CELLS AND AGING
  • 2009-01-22. The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence in LEUKEMIA
  • 2011-03-15. A novel role for CCL3 (MIP-1α) in myeloma-induced bone disease via osteocalcin downregulation and inhibition of osteoblast function in LEUKEMIA
  • 2012-05-29. Functions of DNA methylation: islands, start sites, gene bodies and beyond in NATURE REVIEWS GENETICS
  • 2010-03-21. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia in NATURE
  • 2007-12-25. Inappropriate notch activity and limited mesenchymal stem cell plasticity in the bone marrow of patients with myelodysplastic syndromes in PATHOLOGY & ONCOLOGY RESEARCH
  • 2002-05-01. Functional disturbance of marrow stromal microenvironment in the myelodysplastic syndromes in LEUKEMIA
  • 2009-01-08. Both expanded and uncultured mesenchymal stem cells from MDS patients are genomically abnormal, showing a specific genetic profile for the 5q− syndrome in LEUKEMIA
  • 2012-01-06. Myelodysplastic syndromes: revisiting the role of the bone marrow microenvironment in disease pathogenesis in INTERNATIONAL JOURNAL OF HEMATOLOGY
  • 2011-09-20. Stem Cell Interactions in a Bone Marrow Niche in CURRENT OSTEOPOROSIS REPORTS
  • 2008-02-28. The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites in LEUKEMIA
  • 2009-09-03. Contribution of bone microenvironment to leukemogenesis and leukemia progression in LEUKEMIA
  • 2008-06-25. Epidemiology, classification and prognosis of adults and children with myelodysplastic syndromes in ANNALS OF HEMATOLOGY
  • 2005-02-07. Mesenchymal cells generated from patients with myelodysplastic syndromes are devoid of chromosomal clonal markers and support short- and long-term hematopoiesis in vitro in ONCOGENE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/leu.2013.193

    DOI

    http://dx.doi.org/10.1038/leu.2013.193

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1033380157

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23797473


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Clinical Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Adult", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Aged", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Aged, 80 and over", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Case-Control Studies", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Differentiation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Proliferation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cellular Senescence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cluster Analysis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Colony-Forming Units Assay", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "DNA Methylation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Epigenesis, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Expression Profiling", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Immunophenotyping", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mesenchymal Stem Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Middle Aged", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Myelodysplastic Syndromes", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Osteogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Phenotype", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Geyh", 
            "givenName": "S", 
            "id": "sg:person.0766505315.56", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0766505315.56"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany", 
              "id": "http://www.grid.ac/institutes/grid.509524.f", 
              "name": [
                "Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "\u00d6z", 
            "givenName": "S", 
            "id": "sg:person.010316335107.69", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010316335107.69"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cadeddu", 
            "givenName": "R-P", 
            "id": "sg:person.0725427333.92", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0725427333.92"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fr\u00f6bel", 
            "givenName": "J", 
            "id": "sg:person.0720372115.97", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0720372115.97"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Heidelberg, Germany", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Heidelberg, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Br\u00fcckner", 
            "givenName": "B", 
            "id": "sg:person.0715661407.89", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0715661407.89"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "K\u00fcndgen", 
            "givenName": "A", 
            "id": "sg:person.01107510155.40", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01107510155.40"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fenk", 
            "givenName": "R", 
            "id": "sg:person.01177747626.74", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177747626.74"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bruns", 
            "givenName": "I", 
            "id": "sg:person.01327547615.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01327547615.34"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Orthopedic Surgery, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Orthopedic Surgery, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zilkens", 
            "givenName": "C", 
            "id": "sg:person.01160746056.38", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01160746056.38"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Clinical Chemistry and Laboratory Diagnostics, University Hospital Duesseldorf, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.14778.3d", 
              "name": [
                "Institute for Clinical Chemistry and Laboratory Diagnostics, University Hospital Duesseldorf, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hermsen", 
            "givenName": "D", 
            "id": "sg:person.01041540454.68", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01041540454.68"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gattermann", 
            "givenName": "N", 
            "id": "sg:person.01273447501.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01273447501.34"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kobbe", 
            "givenName": "G", 
            "id": "sg:person.01164073234.53", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01164073234.53"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Germing", 
            "givenName": "U", 
            "id": "sg:person.01362464041.20", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01362464041.20"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "German Cancer Consortium (DKTK)", 
              "id": "http://www.grid.ac/institutes/grid.7497.d", 
              "name": [
                "Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany", 
                "German Cancer Consortium (DKTK)"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lyko", 
            "givenName": "F", 
            "id": "sg:person.01251027364.33", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01251027364.33"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Haas", 
            "givenName": "R", 
            "id": "sg:person.01127414674.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01127414674.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany", 
              "id": "http://www.grid.ac/institutes/grid.411327.2", 
              "name": [
                "Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Schroeder", 
            "givenName": "T", 
            "id": "sg:person.01271136615.68", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01271136615.68"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/leu.2009.175", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045666316", 
              "https://doi.org/10.1038/leu.2009.175"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00277-008-0499-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013497687", 
              "https://doi.org/10.1007/s00277-008-0499-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2011.43", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011106234", 
              "https://doi.org/10.1038/leu.2011.43"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s11914-011-0075-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030672049", 
              "https://doi.org/10.1007/s11914-011-0075-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1208405", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035936742", 
              "https://doi.org/10.1038/sj.onc.1208405"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2008.361", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007441831", 
              "https://doi.org/10.1038/leu.2008.361"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-1-62703-317-6_11", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002762184", 
              "https://doi.org/10.1007/978-1-62703-317-6_11"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s12185-011-1001-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004908166", 
              "https://doi.org/10.1007/s12185-011-1001-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf02940310", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041229633", 
              "https://doi.org/10.1007/bf02940310"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature08851", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003023917", 
              "https://doi.org/10.1038/nature08851"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.leu.2402440", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035624136", 
              "https://doi.org/10.1038/sj.leu.2402440"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2008.48", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044878158", 
              "https://doi.org/10.1038/leu.2008.48"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2008.392", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021573817", 
              "https://doi.org/10.1038/leu.2008.392"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrg3230", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028633739", 
              "https://doi.org/10.1038/nrg3230"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature09262", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022774714", 
              "https://doi.org/10.1038/nature09262"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2013-03-29", 
        "datePublishedReg": "2013-03-29", 
        "description": "Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS\u2013MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS\u2013MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/leu.2013.193", 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1097065", 
            "issn": [
              "0887-6924", 
              "1476-5551"
            ], 
            "name": "Leukemia", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "9", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "27"
          }
        ], 
        "keywords": [
          "MDS-derived mesenchymal stromal cells", 
          "mesenchymal stromal cells", 
          "myelodysplastic syndrome", 
          "MDS-MSCs", 
          "stromal cells", 
          "pathogenesis of MDS", 
          "long-term culture-initiating cell assays", 
          "stromal support", 
          "relevant morbidity", 
          "MDS subtypes", 
          "functional deficits", 
          "healthy controls", 
          "ineffective hematopoiesis", 
          "premature replicative senescence", 
          "cell cycle activity", 
          "reduced expression", 
          "progenitor cells", 
          "altered expression", 
          "proliferative capacity", 
          "key molecules", 
          "cell assay", 
          "kit ligand", 
          "deficient hematopoiesis", 
          "cytochemical staining", 
          "hematopoietic stem", 
          "hematopoiesis", 
          "cells", 
          "replicative senescence", 
          "osteogenic differentiation", 
          "cycle activity", 
          "cellular phenotypes", 
          "morbidity", 
          "patients", 
          "chemokines", 
          "syndrome", 
          "pathogenesis", 
          "expression", 
          "mortality", 
          "angiopoietins", 
          "subtypes", 
          "CD34", 
          "staining", 
          "methylation patterns", 
          "Jagged1", 
          "osteocalcin", 
          "osteopontin", 
          "deficits", 
          "transcriptional regulation", 
          "Osterix", 
          "phenotype", 
          "assays", 
          "specific methylation patterns", 
          "HSPCs", 
          "differentiation", 
          "support", 
          "senescence", 
          "control", 
          "activity", 
          "major characteristics", 
          "biological processes", 
          "regulation", 
          "comprehensive analysis", 
          "patterns", 
          "ability", 
          "MDS results", 
          "analysis", 
          "stem", 
          "results", 
          "growth", 
          "capacity", 
          "characteristics", 
          "molecules", 
          "exhibit", 
          "interaction", 
          "enrichment", 
          "strong enrichment", 
          "contribution", 
          "process"
        ], 
        "name": "Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells", 
        "pagination": "1841-1851", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1033380157"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/leu.2013.193"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "23797473"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/leu.2013.193", 
          "https://app.dimensions.ai/details/publication/pub.1033380157"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-08-04T17:00", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220804/entities/gbq_results/article/article_604.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/leu.2013.193"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/leu.2013.193'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/leu.2013.193'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/leu.2013.193'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/leu.2013.193'


     

    This table displays all metadata directly associated to this object as RDF triples.

    407 TRIPLES      21 PREDICATES      140 URIs      116 LITERALS      28 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/leu.2013.193 schema:about N040c6db0eb7f456684dd561b4259071d
    2 N08ad1938f7a94336a405974aa3aed60d
    3 N0e8ea9faddf14e2fb46ad787fe3e703a
    4 N112b932d79c8483487904fcef7956a65
    5 N240e3439bd9c431fbd15ae70ff470472
    6 N25d81d7abd204e9487541ac0194a3980
    7 N4cf1b9a793cf4b889f79d3f402dcb2a6
    8 N54f322258c7d4802b29dc33247552841
    9 N621e6f9868244953a53920bf47d69ec9
    10 N63f69d892d024fc28476d1d707e382a4
    11 N6527a9bee9c24ea6ac672a7170a92f6c
    12 N6afc8cf2c6114730a86d38d775a0d1c6
    13 N709de0f81d814810a8152750036f85aa
    14 N8b665a5fb7ec4ebe98110d36aff7ea0a
    15 N8bc546f8c704423c9cad82635b332e2c
    16 Nbd2b2b79d52f443195e7dc29908e7a2b
    17 Nc04e32cc307c42a8a2fdb90a91ddd63d
    18 Nd36c4a3f6abd47a587925bd3151eadc9
    19 Ndc546bdbc5a344dd8e627d987d009ce5
    20 Ndd02a2ed0aa94021b757e276d602a7ed
    21 Nf0e1751b7fc940e4bd465ccbd086fe35
    22 anzsrc-for:11
    23 anzsrc-for:1103
    24 anzsrc-for:1112
    25 schema:author N45ec553f2c2c45f6a8aa02c400359600
    26 schema:citation sg:pub.10.1007/978-1-62703-317-6_11
    27 sg:pub.10.1007/bf02940310
    28 sg:pub.10.1007/s00277-008-0499-3
    29 sg:pub.10.1007/s11914-011-0075-y
    30 sg:pub.10.1007/s12185-011-1001-x
    31 sg:pub.10.1038/leu.2008.361
    32 sg:pub.10.1038/leu.2008.392
    33 sg:pub.10.1038/leu.2008.48
    34 sg:pub.10.1038/leu.2009.175
    35 sg:pub.10.1038/leu.2011.43
    36 sg:pub.10.1038/nature08851
    37 sg:pub.10.1038/nature09262
    38 sg:pub.10.1038/nrg3230
    39 sg:pub.10.1038/sj.leu.2402440
    40 sg:pub.10.1038/sj.onc.1208405
    41 schema:datePublished 2013-03-29
    42 schema:datePublishedReg 2013-03-29
    43 schema:description Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS–MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS–MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS.
    44 schema:genre article
    45 schema:isAccessibleForFree false
    46 schema:isPartOf N3cb4f63812474065a529ec24721b2b57
    47 Nf6149fe0d6cb4d3f89e67940f2113e79
    48 sg:journal.1097065
    49 schema:keywords CD34
    50 HSPCs
    51 Jagged1
    52 MDS results
    53 MDS subtypes
    54 MDS-MSCs
    55 MDS-derived mesenchymal stromal cells
    56 Osterix
    57 ability
    58 activity
    59 altered expression
    60 analysis
    61 angiopoietins
    62 assays
    63 biological processes
    64 capacity
    65 cell assay
    66 cell cycle activity
    67 cells
    68 cellular phenotypes
    69 characteristics
    70 chemokines
    71 comprehensive analysis
    72 contribution
    73 control
    74 cycle activity
    75 cytochemical staining
    76 deficient hematopoiesis
    77 deficits
    78 differentiation
    79 enrichment
    80 exhibit
    81 expression
    82 functional deficits
    83 growth
    84 healthy controls
    85 hematopoiesis
    86 hematopoietic stem
    87 ineffective hematopoiesis
    88 interaction
    89 key molecules
    90 kit ligand
    91 long-term culture-initiating cell assays
    92 major characteristics
    93 mesenchymal stromal cells
    94 methylation patterns
    95 molecules
    96 morbidity
    97 mortality
    98 myelodysplastic syndrome
    99 osteocalcin
    100 osteogenic differentiation
    101 osteopontin
    102 pathogenesis
    103 pathogenesis of MDS
    104 patients
    105 patterns
    106 phenotype
    107 premature replicative senescence
    108 process
    109 progenitor cells
    110 proliferative capacity
    111 reduced expression
    112 regulation
    113 relevant morbidity
    114 replicative senescence
    115 results
    116 senescence
    117 specific methylation patterns
    118 staining
    119 stem
    120 stromal cells
    121 stromal support
    122 strong enrichment
    123 subtypes
    124 support
    125 syndrome
    126 transcriptional regulation
    127 schema:name Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells
    128 schema:pagination 1841-1851
    129 schema:productId N076511aa531846a7bfdff48ccc67d625
    130 N2d0e257f5b694876b3a1944f1d8d2ea8
    131 N6d72fe035aa549d19e11fe804b352039
    132 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033380157
    133 https://doi.org/10.1038/leu.2013.193
    134 schema:sdDatePublished 2022-08-04T17:00
    135 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    136 schema:sdPublisher N9fe13006982042c3bc9c2e8c2aaf4cd9
    137 schema:url https://doi.org/10.1038/leu.2013.193
    138 sgo:license sg:explorer/license/
    139 sgo:sdDataset articles
    140 rdf:type schema:ScholarlyArticle
    141 N040c6db0eb7f456684dd561b4259071d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    142 schema:name Cluster Analysis
    143 rdf:type schema:DefinedTerm
    144 N076511aa531846a7bfdff48ccc67d625 schema:name dimensions_id
    145 schema:value pub.1033380157
    146 rdf:type schema:PropertyValue
    147 N07852f9cd7e94dc09eb0171903ffd0f6 rdf:first sg:person.010316335107.69
    148 rdf:rest N0e03485aa57142a597d536b4938e8ccf
    149 N08ad1938f7a94336a405974aa3aed60d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    150 schema:name Phenotype
    151 rdf:type schema:DefinedTerm
    152 N0d43416e4705419e81dde7e648a69108 rdf:first sg:person.01271136615.68
    153 rdf:rest rdf:nil
    154 N0e03485aa57142a597d536b4938e8ccf rdf:first sg:person.0725427333.92
    155 rdf:rest Nd0fa7fa363e1404bafc872d7f0694eea
    156 N0e8ea9faddf14e2fb46ad787fe3e703a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    157 schema:name Myelodysplastic Syndromes
    158 rdf:type schema:DefinedTerm
    159 N112b932d79c8483487904fcef7956a65 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    160 schema:name Cellular Senescence
    161 rdf:type schema:DefinedTerm
    162 N1a9c2ee5526e45629ef960556a0782f1 rdf:first sg:person.01127414674.14
    163 rdf:rest N0d43416e4705419e81dde7e648a69108
    164 N240e3439bd9c431fbd15ae70ff470472 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    165 schema:name Aged
    166 rdf:type schema:DefinedTerm
    167 N25d81d7abd204e9487541ac0194a3980 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    168 schema:name Immunophenotyping
    169 rdf:type schema:DefinedTerm
    170 N2d0e257f5b694876b3a1944f1d8d2ea8 schema:name pubmed_id
    171 schema:value 23797473
    172 rdf:type schema:PropertyValue
    173 N2d6212bedb644e37b2cf681a86846577 rdf:first sg:person.01107510155.40
    174 rdf:rest Nc8ba49f254cb4c4eac82d7bb8431ae63
    175 N3cb4f63812474065a529ec24721b2b57 schema:volumeNumber 27
    176 rdf:type schema:PublicationVolume
    177 N3ce22868c4f646ebaeae7a14dd61e5ed rdf:first sg:person.01041540454.68
    178 rdf:rest N861569f49a724ce186f51f68dbf7edb3
    179 N45ec553f2c2c45f6a8aa02c400359600 rdf:first sg:person.0766505315.56
    180 rdf:rest N07852f9cd7e94dc09eb0171903ffd0f6
    181 N4cf1b9a793cf4b889f79d3f402dcb2a6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    182 schema:name Colony-Forming Units Assay
    183 rdf:type schema:DefinedTerm
    184 N54f322258c7d4802b29dc33247552841 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    185 schema:name Humans
    186 rdf:type schema:DefinedTerm
    187 N621e6f9868244953a53920bf47d69ec9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    188 schema:name Aged, 80 and over
    189 rdf:type schema:DefinedTerm
    190 N63f69d892d024fc28476d1d707e382a4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    191 schema:name Case-Control Studies
    192 rdf:type schema:DefinedTerm
    193 N6527a9bee9c24ea6ac672a7170a92f6c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    194 schema:name Osteogenesis
    195 rdf:type schema:DefinedTerm
    196 N6afc8cf2c6114730a86d38d775a0d1c6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    197 schema:name Adult
    198 rdf:type schema:DefinedTerm
    199 N6d72fe035aa549d19e11fe804b352039 schema:name doi
    200 schema:value 10.1038/leu.2013.193
    201 rdf:type schema:PropertyValue
    202 N6de06a5dafcc47adbb9da6790dbcbc27 rdf:first sg:person.01327547615.34
    203 rdf:rest N913cc9be297d4a0aa78a20673f01541c
    204 N6f819c5a366f47b3b78c2676313695ea rdf:first sg:person.0715661407.89
    205 rdf:rest N2d6212bedb644e37b2cf681a86846577
    206 N709de0f81d814810a8152750036f85aa schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    207 schema:name Cell Differentiation
    208 rdf:type schema:DefinedTerm
    209 N861569f49a724ce186f51f68dbf7edb3 rdf:first sg:person.01273447501.34
    210 rdf:rest Nb2e6b764b5d74d51a00226f1552f2380
    211 N8b665a5fb7ec4ebe98110d36aff7ea0a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    212 schema:name Male
    213 rdf:type schema:DefinedTerm
    214 N8bc546f8c704423c9cad82635b332e2c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    215 schema:name Cell Proliferation
    216 rdf:type schema:DefinedTerm
    217 N913cc9be297d4a0aa78a20673f01541c rdf:first sg:person.01160746056.38
    218 rdf:rest N3ce22868c4f646ebaeae7a14dd61e5ed
    219 N9167ad21963d485a8e03f145b3f99492 rdf:first sg:person.01251027364.33
    220 rdf:rest N1a9c2ee5526e45629ef960556a0782f1
    221 N9fe13006982042c3bc9c2e8c2aaf4cd9 schema:name Springer Nature - SN SciGraph project
    222 rdf:type schema:Organization
    223 Nb2e6b764b5d74d51a00226f1552f2380 rdf:first sg:person.01164073234.53
    224 rdf:rest Nea634ac6649d419e9d8001128c12f285
    225 Nbd2b2b79d52f443195e7dc29908e7a2b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    226 schema:name Middle Aged
    227 rdf:type schema:DefinedTerm
    228 Nc04e32cc307c42a8a2fdb90a91ddd63d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    229 schema:name DNA Methylation
    230 rdf:type schema:DefinedTerm
    231 Nc8ba49f254cb4c4eac82d7bb8431ae63 rdf:first sg:person.01177747626.74
    232 rdf:rest N6de06a5dafcc47adbb9da6790dbcbc27
    233 Nd0fa7fa363e1404bafc872d7f0694eea rdf:first sg:person.0720372115.97
    234 rdf:rest N6f819c5a366f47b3b78c2676313695ea
    235 Nd36c4a3f6abd47a587925bd3151eadc9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    236 schema:name Female
    237 rdf:type schema:DefinedTerm
    238 Ndc546bdbc5a344dd8e627d987d009ce5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    239 schema:name Mesenchymal Stem Cells
    240 rdf:type schema:DefinedTerm
    241 Ndd02a2ed0aa94021b757e276d602a7ed schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    242 schema:name Gene Expression Profiling
    243 rdf:type schema:DefinedTerm
    244 Nea634ac6649d419e9d8001128c12f285 rdf:first sg:person.01362464041.20
    245 rdf:rest N9167ad21963d485a8e03f145b3f99492
    246 Nf0e1751b7fc940e4bd465ccbd086fe35 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    247 schema:name Epigenesis, Genetic
    248 rdf:type schema:DefinedTerm
    249 Nf6149fe0d6cb4d3f89e67940f2113e79 schema:issueNumber 9
    250 rdf:type schema:PublicationIssue
    251 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    252 schema:name Medical and Health Sciences
    253 rdf:type schema:DefinedTerm
    254 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
    255 schema:name Clinical Sciences
    256 rdf:type schema:DefinedTerm
    257 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    258 schema:name Oncology and Carcinogenesis
    259 rdf:type schema:DefinedTerm
    260 sg:journal.1097065 schema:issn 0887-6924
    261 1476-5551
    262 schema:name Leukemia
    263 schema:publisher Springer Nature
    264 rdf:type schema:Periodical
    265 sg:person.010316335107.69 schema:affiliation grid-institutes:grid.509524.f
    266 schema:familyName Öz
    267 schema:givenName S
    268 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010316335107.69
    269 rdf:type schema:Person
    270 sg:person.01041540454.68 schema:affiliation grid-institutes:grid.14778.3d
    271 schema:familyName Hermsen
    272 schema:givenName D
    273 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01041540454.68
    274 rdf:type schema:Person
    275 sg:person.01107510155.40 schema:affiliation grid-institutes:grid.411327.2
    276 schema:familyName Kündgen
    277 schema:givenName A
    278 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01107510155.40
    279 rdf:type schema:Person
    280 sg:person.01127414674.14 schema:affiliation grid-institutes:grid.411327.2
    281 schema:familyName Haas
    282 schema:givenName R
    283 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01127414674.14
    284 rdf:type schema:Person
    285 sg:person.01160746056.38 schema:affiliation grid-institutes:grid.411327.2
    286 schema:familyName Zilkens
    287 schema:givenName C
    288 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01160746056.38
    289 rdf:type schema:Person
    290 sg:person.01164073234.53 schema:affiliation grid-institutes:grid.411327.2
    291 schema:familyName Kobbe
    292 schema:givenName G
    293 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01164073234.53
    294 rdf:type schema:Person
    295 sg:person.01177747626.74 schema:affiliation grid-institutes:grid.411327.2
    296 schema:familyName Fenk
    297 schema:givenName R
    298 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177747626.74
    299 rdf:type schema:Person
    300 sg:person.01251027364.33 schema:affiliation grid-institutes:grid.7497.d
    301 schema:familyName Lyko
    302 schema:givenName F
    303 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01251027364.33
    304 rdf:type schema:Person
    305 sg:person.01271136615.68 schema:affiliation grid-institutes:grid.411327.2
    306 schema:familyName Schroeder
    307 schema:givenName T
    308 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01271136615.68
    309 rdf:type schema:Person
    310 sg:person.01273447501.34 schema:affiliation grid-institutes:grid.411327.2
    311 schema:familyName Gattermann
    312 schema:givenName N
    313 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01273447501.34
    314 rdf:type schema:Person
    315 sg:person.01327547615.34 schema:affiliation grid-institutes:grid.411327.2
    316 schema:familyName Bruns
    317 schema:givenName I
    318 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01327547615.34
    319 rdf:type schema:Person
    320 sg:person.01362464041.20 schema:affiliation grid-institutes:grid.411327.2
    321 schema:familyName Germing
    322 schema:givenName U
    323 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01362464041.20
    324 rdf:type schema:Person
    325 sg:person.0715661407.89 schema:affiliation grid-institutes:None
    326 schema:familyName Brückner
    327 schema:givenName B
    328 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0715661407.89
    329 rdf:type schema:Person
    330 sg:person.0720372115.97 schema:affiliation grid-institutes:grid.411327.2
    331 schema:familyName Fröbel
    332 schema:givenName J
    333 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0720372115.97
    334 rdf:type schema:Person
    335 sg:person.0725427333.92 schema:affiliation grid-institutes:grid.411327.2
    336 schema:familyName Cadeddu
    337 schema:givenName R-P
    338 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0725427333.92
    339 rdf:type schema:Person
    340 sg:person.0766505315.56 schema:affiliation grid-institutes:grid.411327.2
    341 schema:familyName Geyh
    342 schema:givenName S
    343 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0766505315.56
    344 rdf:type schema:Person
    345 sg:pub.10.1007/978-1-62703-317-6_11 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002762184
    346 https://doi.org/10.1007/978-1-62703-317-6_11
    347 rdf:type schema:CreativeWork
    348 sg:pub.10.1007/bf02940310 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041229633
    349 https://doi.org/10.1007/bf02940310
    350 rdf:type schema:CreativeWork
    351 sg:pub.10.1007/s00277-008-0499-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013497687
    352 https://doi.org/10.1007/s00277-008-0499-3
    353 rdf:type schema:CreativeWork
    354 sg:pub.10.1007/s11914-011-0075-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1030672049
    355 https://doi.org/10.1007/s11914-011-0075-y
    356 rdf:type schema:CreativeWork
    357 sg:pub.10.1007/s12185-011-1001-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1004908166
    358 https://doi.org/10.1007/s12185-011-1001-x
    359 rdf:type schema:CreativeWork
    360 sg:pub.10.1038/leu.2008.361 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007441831
    361 https://doi.org/10.1038/leu.2008.361
    362 rdf:type schema:CreativeWork
    363 sg:pub.10.1038/leu.2008.392 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021573817
    364 https://doi.org/10.1038/leu.2008.392
    365 rdf:type schema:CreativeWork
    366 sg:pub.10.1038/leu.2008.48 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044878158
    367 https://doi.org/10.1038/leu.2008.48
    368 rdf:type schema:CreativeWork
    369 sg:pub.10.1038/leu.2009.175 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045666316
    370 https://doi.org/10.1038/leu.2009.175
    371 rdf:type schema:CreativeWork
    372 sg:pub.10.1038/leu.2011.43 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011106234
    373 https://doi.org/10.1038/leu.2011.43
    374 rdf:type schema:CreativeWork
    375 sg:pub.10.1038/nature08851 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003023917
    376 https://doi.org/10.1038/nature08851
    377 rdf:type schema:CreativeWork
    378 sg:pub.10.1038/nature09262 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022774714
    379 https://doi.org/10.1038/nature09262
    380 rdf:type schema:CreativeWork
    381 sg:pub.10.1038/nrg3230 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028633739
    382 https://doi.org/10.1038/nrg3230
    383 rdf:type schema:CreativeWork
    384 sg:pub.10.1038/sj.leu.2402440 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035624136
    385 https://doi.org/10.1038/sj.leu.2402440
    386 rdf:type schema:CreativeWork
    387 sg:pub.10.1038/sj.onc.1208405 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035936742
    388 https://doi.org/10.1038/sj.onc.1208405
    389 rdf:type schema:CreativeWork
    390 grid-institutes:None schema:alternateName Heidelberg, Germany
    391 schema:name Heidelberg, Germany
    392 rdf:type schema:Organization
    393 grid-institutes:grid.14778.3d schema:alternateName Institute for Clinical Chemistry and Laboratory Diagnostics, University Hospital Duesseldorf, Duesseldorf, Germany
    394 schema:name Institute for Clinical Chemistry and Laboratory Diagnostics, University Hospital Duesseldorf, Duesseldorf, Germany
    395 rdf:type schema:Organization
    396 grid-institutes:grid.411327.2 schema:alternateName Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany
    397 Department of Orthopedic Surgery, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany
    398 schema:name Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany
    399 Department of Orthopedic Surgery, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany
    400 rdf:type schema:Organization
    401 grid-institutes:grid.509524.f schema:alternateName Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany
    402 schema:name Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany
    403 rdf:type schema:Organization
    404 grid-institutes:grid.7497.d schema:alternateName German Cancer Consortium (DKTK)
    405 schema:name Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany
    406 German Cancer Consortium (DKTK)
    407 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...