A unique role of p53 haploinsufficiency or loss in the development of acute myeloid leukemia with FLT3-ITD mutation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-11-03

AUTHORS

Min Yang, Zengkai Pan, Kezhi Huang, Guntram Büsche, Hongyun Liu, Gudrun Göhring, Regina Rumpel, Oliver Dittrich-Breiholz, Steven Talbot, Michaela Scherr, Anuhar Chaturvedi, Matthias Eder, Julia Skokowa, Jianfeng Zhou, Karl Welte, Nils von Neuhoff, Ligen Liu, Arnold Ganser, Zhixiong Li

ABSTRACT

With an incidence of ~50%, the absence or reduced protein level of p53 is much more common than TP53 mutations in acute myeloid leukemia (AML). AML with FLT3-ITD (internal tandem duplication) mutations has an unfavorable prognosis and is highly associated with wt-p53 dysfunction. While TP53 mutation in the presence of FLT3-ITD does not induce AML in mice, it is not clear whether p53 haploinsufficiency or loss cooperates with FLT3-ITD in the induction of AML. Here, we generated FLT3-ITD knock-in; p53 knockout (heterozygous and homozygous) double-transgenic mice and found that both alterations strongly cooperated in the induction of cytogenetically normal AML without increasing the self-renewal potential. At the molecular level, we found the strong upregulation of Htra3 and the downregulation of Lin28a, leading to enhanced proliferation and the inhibition of apoptosis and differentiation. The co-occurrence of Htra3 overexpression and Lin28a knockdown, in the presence of FLT3-ITD, induced AML with similar morphology as leukemic cells from double-transgenic mice. These leukemic cells were highly sensitive to the proteasome inhibitor carfilzomib. Carfilzomib strongly enhanced the activity of targeting AXL (upstream of FLT3) against murine and human leukemic cells. Our results unravel a unique role of p53 haploinsufficiency or loss in the development of FLT3-ITD + AML. More... »

PAGES

675-686

References to SciGraph publications

  • 2001-05-01. Proliferation, cell cycle and apoptosis in cancer in NATURE
  • 2016-11-25. p53 pathway dysfunction is highly prevalent in acute myeloid leukemia independent of TP53 mutational status in LEUKEMIA
  • 2017-01-10. Giving AXL the axe: targeting AXL in human malignancy in BRITISH JOURNAL OF CANCER
  • 2019-01-23. Mutant p53 enhances leukemia-initiating cell self-renewal to promote leukemia development in LEUKEMIA
  • 2016-02-19. Leukemogenic potency of the novel FLT3-N676K mutant in ANNALS OF HEMATOLOGY
  • 2013-01-10. Morphology and quantitative composition of hematopoietic cells in murine bone marrow and spleen of healthy subjects in ANNALS OF HEMATOLOGY
  • 2014-12-05. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 in GENOME BIOLOGY
  • 2009-01-08. The prognostic impact of 17p (p53) deletion in 2272 adults with acute myeloid leukemia in LEUKEMIA
  • 2016-06-27. Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer in NATURE CELL BIOLOGY
  • 2013-03-12. A powerful molecular synergy between mutant Nucleophosmin and Flt3-ITD drives acute myeloid leukemia in mice in LEUKEMIA
  • 2007-04-08. p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM in NATURE CELL BIOLOGY
  • 2020-05-13. p53: 800 million years of evolution and 40 years of discovery in NATURE REVIEWS CANCER
  • 2017-02-08. p190-B RhoGAP and intracellular cytokine signals balance hematopoietic stem and progenitor cell self-renewal and differentiation in NATURE COMMUNICATIONS
  • Journal

    TITLE

    Leukemia

    ISSUE

    3

    VOLUME

    36

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41375-021-01452-6

    DOI

    http://dx.doi.org/10.1038/s41375-021-01452-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1142336221

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34732858


    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/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Duplication", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Expression Regulation, Leukemic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Knock-In Techniques", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Haploinsufficiency", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Leukemia, Myeloid, Acute", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice, Inbred C57BL", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tumor Suppressor Protein p53", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "fms-Like Tyrosine Kinase 3", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yang", 
            "givenName": "Min", 
            "id": "sg:person.01335614764.96", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01335614764.96"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China", 
              "id": "http://www.grid.ac/institutes/grid.16821.3c", 
              "name": [
                "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany", 
                "National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Pan", 
            "givenName": "Zengkai", 
            "id": "sg:person.01142303631.25", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01142303631.25"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, and Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China", 
              "id": "http://www.grid.ac/institutes/grid.412536.7", 
              "name": [
                "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany", 
                "Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, and Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Huang", 
            "givenName": "Kezhi", 
            "id": "sg:person.01120435714.92", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01120435714.92"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute of Pathology, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Institute of Pathology, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "B\u00fcsche", 
            "givenName": "Guntram", 
            "id": "sg:person.01114275705.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01114275705.34"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Liu", 
            "givenName": "Hongyun", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Human Genetics, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Department of Human Genetics, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "G\u00f6hring", 
            "givenName": "Gudrun", 
            "id": "sg:person.01257266136.63", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257266136.63"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rumpel", 
            "givenName": "Regina", 
            "id": "sg:person.01305644405.46", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01305644405.46"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Research Core Unit Genomics, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Research Core Unit Genomics, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Dittrich-Breiholz", 
            "givenName": "Oliver", 
            "id": "sg:person.0651163647.26", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0651163647.26"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Talbot", 
            "givenName": "Steven", 
            "id": "sg:person.012002221623.35", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012002221623.35"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Scherr", 
            "givenName": "Michaela", 
            "id": "sg:person.0603313157.42", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0603313157.42"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chaturvedi", 
            "givenName": "Anuhar", 
            "id": "sg:person.0636314430.55", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0636314430.55"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Eder", 
            "givenName": "Matthias", 
            "id": "sg:person.0763175305.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0763175305.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Oncology, Clinical Immunology, University of T\u00fcbingen, T\u00fcbingen, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10392.39", 
              "name": [
                "Department of Hematology, Oncology, Clinical Immunology, University of T\u00fcbingen, T\u00fcbingen, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Skokowa", 
            "givenName": "Julia", 
            "id": "sg:person.0714007763.08", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0714007763.08"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China", 
              "id": "http://www.grid.ac/institutes/grid.412793.a", 
              "name": [
                "Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zhou", 
            "givenName": "Jianfeng", 
            "id": "sg:person.01273127463.48", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01273127463.48"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University Children\u2019s Hospital, Department of General Pediatrics and Pediatric Hematology and Oncology, T\u00fcbingen, Germany", 
              "id": "http://www.grid.ac/institutes/grid.488549.c", 
              "name": [
                "University Children\u2019s Hospital, Department of General Pediatrics and Pediatric Hematology and Oncology, T\u00fcbingen, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Welte", 
            "givenName": "Karl", 
            "id": "sg:person.0706072733.35", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0706072733.35"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "AML Diagnostic Laboratory, Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany", 
              "id": "http://www.grid.ac/institutes/grid.5718.b", 
              "name": [
                "AML Diagnostic Laboratory, Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "von Neuhoff", 
            "givenName": "Nils", 
            "id": "sg:person.0662646705.67", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0662646705.67"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China", 
              "id": "http://www.grid.ac/institutes/grid.459910.0", 
              "name": [
                "Department of Hematology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Liu", 
            "givenName": "Ligen", 
            "id": "sg:person.011162760717.61", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011162760717.61"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ganser", 
            "givenName": "Arnold", 
            "id": "sg:person.01225227464.09", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01225227464.09"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany", 
              "id": "http://www.grid.ac/institutes/grid.10423.34", 
              "name": [
                "Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Li", 
            "givenName": "Zhixiong", 
            "id": "sg:person.01137575461.44", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01137575461.44"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/s41375-019-0377-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1111616404", 
              "https://doi.org/10.1038/s41375-019-0377-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2013.77", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023022291", 
              "https://doi.org/10.1038/leu.2013.77"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.2016.428", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015580048", 
              "https://doi.org/10.1038/bjc.2016.428"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms14382", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1083733644", 
              "https://doi.org/10.1038/ncomms14382"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13059-014-0550-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015222646", 
              "https://doi.org/10.1186/s13059-014-0550-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2016.350", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034557565", 
              "https://doi.org/10.1038/leu.2016.350"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncb3380", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012428907", 
              "https://doi.org/10.1038/ncb3380"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00277-012-1653-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019000608", 
              "https://doi.org/10.1007/s00277-012-1653-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncb1571", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041654071", 
              "https://doi.org/10.1038/ncb1571"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2008.375", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050868040", 
              "https://doi.org/10.1038/leu.2008.375"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00277-016-2616-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010663437", 
              "https://doi.org/10.1007/s00277-016-2616-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41568-020-0262-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1127544291", 
              "https://doi.org/10.1038/s41568-020-0262-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35077213", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042524556", 
              "https://doi.org/10.1038/35077213"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2021-11-03", 
        "datePublishedReg": "2021-11-03", 
        "description": "With an incidence of ~50%, the absence or reduced protein level of p53 is much more common than TP53 mutations in acute myeloid leukemia (AML). AML with FLT3-ITD (internal tandem duplication) mutations has an unfavorable prognosis and is highly associated with wt-p53 dysfunction. While TP53 mutation in the presence of FLT3-ITD does not induce AML in mice, it is not clear whether p53 haploinsufficiency or loss cooperates with FLT3-ITD in the induction of AML. Here, we generated FLT3-ITD knock-in; p53 knockout (heterozygous and homozygous) double-transgenic mice and found that both alterations strongly cooperated in the induction of cytogenetically normal AML without increasing the self-renewal potential. At the molecular level, we found the strong upregulation of Htra3 and the downregulation of Lin28a, leading to enhanced proliferation and the inhibition of apoptosis and differentiation. The co-occurrence of Htra3 overexpression and Lin28a knockdown, in the presence of FLT3-ITD, induced AML with similar morphology as leukemic cells from double-transgenic mice. These leukemic cells were highly sensitive to the proteasome inhibitor carfilzomib. Carfilzomib strongly enhanced the activity of targeting AXL (upstream of FLT3) against murine and human leukemic cells. Our results unravel a unique role of p53 haploinsufficiency or loss in the development of FLT3-ITD\u2009+\u2009AML.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41375-021-01452-6", 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1097065", 
            "issn": [
              "0887-6924", 
              "1476-5551"
            ], 
            "name": "Leukemia", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "3", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "36"
          }
        ], 
        "keywords": [
          "acute myeloid leukemia", 
          "FLT3-ITD mutation", 
          "double transgenic mice", 
          "FLT3-ITD", 
          "p53 haploinsufficiency", 
          "leukemic cells", 
          "myeloid leukemia", 
          "TP53 mutations", 
          "normal acute myeloid leukemia", 
          "FLT3-ITD knock", 
          "proteasome inhibitor carfilzomib", 
          "induction of AML", 
          "human leukemic cells", 
          "unfavorable prognosis", 
          "inhibition of apoptosis", 
          "enhanced proliferation", 
          "protein levels", 
          "mice", 
          "Lin28a knockdown", 
          "self-renewal potential", 
          "strong upregulation", 
          "carfilzomib", 
          "unique role", 
          "leukemia", 
          "haploinsufficiency", 
          "cells", 
          "induction", 
          "mutations", 
          "prognosis", 
          "dysfunction", 
          "incidence", 
          "Axl", 
          "upregulation", 
          "downregulation", 
          "levels", 
          "p53", 
          "murine", 
          "apoptosis", 
          "inhibition", 
          "knockdown", 
          "proliferation", 
          "alterations", 
          "role", 
          "overexpression", 
          "HtrA3", 
          "loss", 
          "LIN28A", 
          "molecular level", 
          "presence", 
          "differentiation", 
          "absence", 
          "knock", 
          "similar morphology", 
          "activity", 
          "development", 
          "cooperate", 
          "potential", 
          "results", 
          "morphology"
        ], 
        "name": "A unique role of p53 haploinsufficiency or loss in the development of acute myeloid leukemia with FLT3-ITD mutation", 
        "pagination": "675-686", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1142336221"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41375-021-01452-6"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "34732858"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41375-021-01452-6", 
          "https://app.dimensions.ai/details/publication/pub.1142336221"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-12-01T06:42", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221201/entities/gbq_results/article/article_894.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41375-021-01452-6"
      }
    ]
     

    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/s41375-021-01452-6'

    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/s41375-021-01452-6'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41375-021-01452-6'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41375-021-01452-6'


     

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

    372 TRIPLES      21 PREDICATES      108 URIs      87 LITERALS      18 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41375-021-01452-6 schema:about N54ab97fab5114ec49053d1bb119343e2
    2 N5862dc4709324f1caf748806d0c5fe22
    3 N7671e6f6607f4e0b8d2e714d3baa6206
    4 N8cdf52bc7fa84bf58b1c088a6792ba31
    5 N90914bc382714802ac23c9c799d6d17b
    6 N9c4bb4e22f554f9b94714cc4a68e6c28
    7 Nb0e61cc66ea84e02bbc8f7ddb08dbd1e
    8 Nb4fb52c7b2aa46f59577839cfdf6d11a
    9 Nc7f30e4ce4d14d4aa2a99ec434744a92
    10 Nc831186218f64e11984644f683e22793
    11 Nf7d7f66db32345e0a6ac4fbaef667160
    12 anzsrc-for:11
    13 anzsrc-for:1112
    14 schema:author N87e69129e9874e36aec77154e1a112a1
    15 schema:citation sg:pub.10.1007/s00277-012-1653-5
    16 sg:pub.10.1007/s00277-016-2616-z
    17 sg:pub.10.1038/35077213
    18 sg:pub.10.1038/bjc.2016.428
    19 sg:pub.10.1038/leu.2008.375
    20 sg:pub.10.1038/leu.2013.77
    21 sg:pub.10.1038/leu.2016.350
    22 sg:pub.10.1038/ncb1571
    23 sg:pub.10.1038/ncb3380
    24 sg:pub.10.1038/ncomms14382
    25 sg:pub.10.1038/s41375-019-0377-0
    26 sg:pub.10.1038/s41568-020-0262-1
    27 sg:pub.10.1186/s13059-014-0550-8
    28 schema:datePublished 2021-11-03
    29 schema:datePublishedReg 2021-11-03
    30 schema:description With an incidence of ~50%, the absence or reduced protein level of p53 is much more common than TP53 mutations in acute myeloid leukemia (AML). AML with FLT3-ITD (internal tandem duplication) mutations has an unfavorable prognosis and is highly associated with wt-p53 dysfunction. While TP53 mutation in the presence of FLT3-ITD does not induce AML in mice, it is not clear whether p53 haploinsufficiency or loss cooperates with FLT3-ITD in the induction of AML. Here, we generated FLT3-ITD knock-in; p53 knockout (heterozygous and homozygous) double-transgenic mice and found that both alterations strongly cooperated in the induction of cytogenetically normal AML without increasing the self-renewal potential. At the molecular level, we found the strong upregulation of Htra3 and the downregulation of Lin28a, leading to enhanced proliferation and the inhibition of apoptosis and differentiation. The co-occurrence of Htra3 overexpression and Lin28a knockdown, in the presence of FLT3-ITD, induced AML with similar morphology as leukemic cells from double-transgenic mice. These leukemic cells were highly sensitive to the proteasome inhibitor carfilzomib. Carfilzomib strongly enhanced the activity of targeting AXL (upstream of FLT3) against murine and human leukemic cells. Our results unravel a unique role of p53 haploinsufficiency or loss in the development of FLT3-ITD + AML.
    31 schema:genre article
    32 schema:isAccessibleForFree true
    33 schema:isPartOf N523fa654152847aca9919223d58b59a4
    34 Ncd711b189fc54e45a87c4b2b15ef05a8
    35 sg:journal.1097065
    36 schema:keywords Axl
    37 FLT3-ITD
    38 FLT3-ITD knock
    39 FLT3-ITD mutation
    40 HtrA3
    41 LIN28A
    42 Lin28a knockdown
    43 TP53 mutations
    44 absence
    45 activity
    46 acute myeloid leukemia
    47 alterations
    48 apoptosis
    49 carfilzomib
    50 cells
    51 cooperate
    52 development
    53 differentiation
    54 double transgenic mice
    55 downregulation
    56 dysfunction
    57 enhanced proliferation
    58 haploinsufficiency
    59 human leukemic cells
    60 incidence
    61 induction
    62 induction of AML
    63 inhibition
    64 inhibition of apoptosis
    65 knock
    66 knockdown
    67 leukemia
    68 leukemic cells
    69 levels
    70 loss
    71 mice
    72 molecular level
    73 morphology
    74 murine
    75 mutations
    76 myeloid leukemia
    77 normal acute myeloid leukemia
    78 overexpression
    79 p53
    80 p53 haploinsufficiency
    81 potential
    82 presence
    83 prognosis
    84 proliferation
    85 proteasome inhibitor carfilzomib
    86 protein levels
    87 results
    88 role
    89 self-renewal potential
    90 similar morphology
    91 strong upregulation
    92 unfavorable prognosis
    93 unique role
    94 upregulation
    95 schema:name A unique role of p53 haploinsufficiency or loss in the development of acute myeloid leukemia with FLT3-ITD mutation
    96 schema:pagination 675-686
    97 schema:productId N1d3eecc40ebf428dbedf384bfcfe513c
    98 N32cb9aaf67a54270aed72eed00b6304f
    99 N7a4e34f3e5c44dbeacf5361c68c623f2
    100 schema:sameAs https://app.dimensions.ai/details/publication/pub.1142336221
    101 https://doi.org/10.1038/s41375-021-01452-6
    102 schema:sdDatePublished 2022-12-01T06:42
    103 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    104 schema:sdPublisher Nbecb008579a346ffaf546baeec7b31b8
    105 schema:url https://doi.org/10.1038/s41375-021-01452-6
    106 sgo:license sg:explorer/license/
    107 sgo:sdDataset articles
    108 rdf:type schema:ScholarlyArticle
    109 N0026837e3654414db919d412669f1830 rdf:first sg:person.01120435714.92
    110 rdf:rest Na09353c313d249218b776a7e13cdb1f2
    111 N03fe4471ad5d4b45b0aba609252998d4 schema:affiliation grid-institutes:grid.10423.34
    112 schema:familyName Liu
    113 schema:givenName Hongyun
    114 rdf:type schema:Person
    115 N057022a20cf142f2a479911b80760a53 rdf:first sg:person.0763175305.45
    116 rdf:rest N9ab3f361962342efabaa1cea491b7784
    117 N073ecb2138884bf79318a258498db2ef rdf:first sg:person.01305644405.46
    118 rdf:rest Ne4d982e3b1b745249f1914e793029f99
    119 N1bacef9dd53048dbbd7b47336d8eb38b rdf:first sg:person.012002221623.35
    120 rdf:rest N4e673a63e9d249fea7f562888e677eeb
    121 N1d3eecc40ebf428dbedf384bfcfe513c schema:name doi
    122 schema:value 10.1038/s41375-021-01452-6
    123 rdf:type schema:PropertyValue
    124 N1ee2e0b5fb1b41a19abc8162b41f84ba rdf:first sg:person.01257266136.63
    125 rdf:rest N073ecb2138884bf79318a258498db2ef
    126 N23b577d15c7b454fa966cf90c970f8fb rdf:first sg:person.01225227464.09
    127 rdf:rest Nd6367ebef7324df5be07391ba56c8fc3
    128 N32cb9aaf67a54270aed72eed00b6304f schema:name dimensions_id
    129 schema:value pub.1142336221
    130 rdf:type schema:PropertyValue
    131 N3c89e56a28d041229606ebdc5601c303 rdf:first sg:person.0636314430.55
    132 rdf:rest N057022a20cf142f2a479911b80760a53
    133 N4e673a63e9d249fea7f562888e677eeb rdf:first sg:person.0603313157.42
    134 rdf:rest N3c89e56a28d041229606ebdc5601c303
    135 N4fbf68082bb74626afc44cbd6ba61215 rdf:first sg:person.0706072733.35
    136 rdf:rest Nb01be3cdd64746bbb9cdf6497efa7f47
    137 N523fa654152847aca9919223d58b59a4 schema:issueNumber 3
    138 rdf:type schema:PublicationIssue
    139 N54ab97fab5114ec49053d1bb119343e2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    140 schema:name fms-Like Tyrosine Kinase 3
    141 rdf:type schema:DefinedTerm
    142 N5862dc4709324f1caf748806d0c5fe22 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    143 schema:name Mutation
    144 rdf:type schema:DefinedTerm
    145 N7671e6f6607f4e0b8d2e714d3baa6206 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    146 schema:name Gene Expression Regulation, Leukemic
    147 rdf:type schema:DefinedTerm
    148 N7a4e34f3e5c44dbeacf5361c68c623f2 schema:name pubmed_id
    149 schema:value 34732858
    150 rdf:type schema:PropertyValue
    151 N7eff7ea3726744e58663eda6ed7cf80a rdf:first sg:person.011162760717.61
    152 rdf:rest N23b577d15c7b454fa966cf90c970f8fb
    153 N87e69129e9874e36aec77154e1a112a1 rdf:first sg:person.01335614764.96
    154 rdf:rest Nd574afdfa3bd40719e388571f0656812
    155 N8cdf52bc7fa84bf58b1c088a6792ba31 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    156 schema:name Leukemia, Myeloid, Acute
    157 rdf:type schema:DefinedTerm
    158 N90914bc382714802ac23c9c799d6d17b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    159 schema:name Tumor Suppressor Protein p53
    160 rdf:type schema:DefinedTerm
    161 N9ab3f361962342efabaa1cea491b7784 rdf:first sg:person.0714007763.08
    162 rdf:rest Nfadf6159d1ab4da983c4e7f241c01124
    163 N9c4bb4e22f554f9b94714cc4a68e6c28 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    164 schema:name Haploinsufficiency
    165 rdf:type schema:DefinedTerm
    166 Na09353c313d249218b776a7e13cdb1f2 rdf:first sg:person.01114275705.34
    167 rdf:rest Na8eb4be5c2f54553bbcacd5ebc4adfc7
    168 Na8eb4be5c2f54553bbcacd5ebc4adfc7 rdf:first N03fe4471ad5d4b45b0aba609252998d4
    169 rdf:rest N1ee2e0b5fb1b41a19abc8162b41f84ba
    170 Nb01be3cdd64746bbb9cdf6497efa7f47 rdf:first sg:person.0662646705.67
    171 rdf:rest N7eff7ea3726744e58663eda6ed7cf80a
    172 Nb0e61cc66ea84e02bbc8f7ddb08dbd1e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    173 schema:name Mice, Inbred C57BL
    174 rdf:type schema:DefinedTerm
    175 Nb4fb52c7b2aa46f59577839cfdf6d11a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    176 schema:name Gene Duplication
    177 rdf:type schema:DefinedTerm
    178 Nbecb008579a346ffaf546baeec7b31b8 schema:name Springer Nature - SN SciGraph project
    179 rdf:type schema:Organization
    180 Nc7f30e4ce4d14d4aa2a99ec434744a92 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    181 schema:name Mice
    182 rdf:type schema:DefinedTerm
    183 Nc831186218f64e11984644f683e22793 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    184 schema:name Animals
    185 rdf:type schema:DefinedTerm
    186 Ncd711b189fc54e45a87c4b2b15ef05a8 schema:volumeNumber 36
    187 rdf:type schema:PublicationVolume
    188 Nd574afdfa3bd40719e388571f0656812 rdf:first sg:person.01142303631.25
    189 rdf:rest N0026837e3654414db919d412669f1830
    190 Nd6367ebef7324df5be07391ba56c8fc3 rdf:first sg:person.01137575461.44
    191 rdf:rest rdf:nil
    192 Ne4d982e3b1b745249f1914e793029f99 rdf:first sg:person.0651163647.26
    193 rdf:rest N1bacef9dd53048dbbd7b47336d8eb38b
    194 Nf7d7f66db32345e0a6ac4fbaef667160 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    195 schema:name Gene Knock-In Techniques
    196 rdf:type schema:DefinedTerm
    197 Nfadf6159d1ab4da983c4e7f241c01124 rdf:first sg:person.01273127463.48
    198 rdf:rest N4fbf68082bb74626afc44cbd6ba61215
    199 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    200 schema:name Medical and Health Sciences
    201 rdf:type schema:DefinedTerm
    202 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    203 schema:name Oncology and Carcinogenesis
    204 rdf:type schema:DefinedTerm
    205 sg:journal.1097065 schema:issn 0887-6924
    206 1476-5551
    207 schema:name Leukemia
    208 schema:publisher Springer Nature
    209 rdf:type schema:Periodical
    210 sg:person.01114275705.34 schema:affiliation grid-institutes:grid.10423.34
    211 schema:familyName Büsche
    212 schema:givenName Guntram
    213 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01114275705.34
    214 rdf:type schema:Person
    215 sg:person.011162760717.61 schema:affiliation grid-institutes:grid.459910.0
    216 schema:familyName Liu
    217 schema:givenName Ligen
    218 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011162760717.61
    219 rdf:type schema:Person
    220 sg:person.01120435714.92 schema:affiliation grid-institutes:grid.412536.7
    221 schema:familyName Huang
    222 schema:givenName Kezhi
    223 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01120435714.92
    224 rdf:type schema:Person
    225 sg:person.01137575461.44 schema:affiliation grid-institutes:grid.10423.34
    226 schema:familyName Li
    227 schema:givenName Zhixiong
    228 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01137575461.44
    229 rdf:type schema:Person
    230 sg:person.01142303631.25 schema:affiliation grid-institutes:grid.16821.3c
    231 schema:familyName Pan
    232 schema:givenName Zengkai
    233 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01142303631.25
    234 rdf:type schema:Person
    235 sg:person.012002221623.35 schema:affiliation grid-institutes:grid.10423.34
    236 schema:familyName Talbot
    237 schema:givenName Steven
    238 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012002221623.35
    239 rdf:type schema:Person
    240 sg:person.01225227464.09 schema:affiliation grid-institutes:grid.10423.34
    241 schema:familyName Ganser
    242 schema:givenName Arnold
    243 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01225227464.09
    244 rdf:type schema:Person
    245 sg:person.01257266136.63 schema:affiliation grid-institutes:grid.10423.34
    246 schema:familyName Göhring
    247 schema:givenName Gudrun
    248 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257266136.63
    249 rdf:type schema:Person
    250 sg:person.01273127463.48 schema:affiliation grid-institutes:grid.412793.a
    251 schema:familyName Zhou
    252 schema:givenName Jianfeng
    253 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01273127463.48
    254 rdf:type schema:Person
    255 sg:person.01305644405.46 schema:affiliation grid-institutes:grid.10423.34
    256 schema:familyName Rumpel
    257 schema:givenName Regina
    258 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01305644405.46
    259 rdf:type schema:Person
    260 sg:person.01335614764.96 schema:affiliation grid-institutes:grid.10423.34
    261 schema:familyName Yang
    262 schema:givenName Min
    263 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01335614764.96
    264 rdf:type schema:Person
    265 sg:person.0603313157.42 schema:affiliation grid-institutes:grid.10423.34
    266 schema:familyName Scherr
    267 schema:givenName Michaela
    268 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0603313157.42
    269 rdf:type schema:Person
    270 sg:person.0636314430.55 schema:affiliation grid-institutes:grid.10423.34
    271 schema:familyName Chaturvedi
    272 schema:givenName Anuhar
    273 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0636314430.55
    274 rdf:type schema:Person
    275 sg:person.0651163647.26 schema:affiliation grid-institutes:grid.10423.34
    276 schema:familyName Dittrich-Breiholz
    277 schema:givenName Oliver
    278 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0651163647.26
    279 rdf:type schema:Person
    280 sg:person.0662646705.67 schema:affiliation grid-institutes:grid.5718.b
    281 schema:familyName von Neuhoff
    282 schema:givenName Nils
    283 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0662646705.67
    284 rdf:type schema:Person
    285 sg:person.0706072733.35 schema:affiliation grid-institutes:grid.488549.c
    286 schema:familyName Welte
    287 schema:givenName Karl
    288 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0706072733.35
    289 rdf:type schema:Person
    290 sg:person.0714007763.08 schema:affiliation grid-institutes:grid.10392.39
    291 schema:familyName Skokowa
    292 schema:givenName Julia
    293 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0714007763.08
    294 rdf:type schema:Person
    295 sg:person.0763175305.45 schema:affiliation grid-institutes:grid.10423.34
    296 schema:familyName Eder
    297 schema:givenName Matthias
    298 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0763175305.45
    299 rdf:type schema:Person
    300 sg:pub.10.1007/s00277-012-1653-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019000608
    301 https://doi.org/10.1007/s00277-012-1653-5
    302 rdf:type schema:CreativeWork
    303 sg:pub.10.1007/s00277-016-2616-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1010663437
    304 https://doi.org/10.1007/s00277-016-2616-z
    305 rdf:type schema:CreativeWork
    306 sg:pub.10.1038/35077213 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042524556
    307 https://doi.org/10.1038/35077213
    308 rdf:type schema:CreativeWork
    309 sg:pub.10.1038/bjc.2016.428 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015580048
    310 https://doi.org/10.1038/bjc.2016.428
    311 rdf:type schema:CreativeWork
    312 sg:pub.10.1038/leu.2008.375 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050868040
    313 https://doi.org/10.1038/leu.2008.375
    314 rdf:type schema:CreativeWork
    315 sg:pub.10.1038/leu.2013.77 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023022291
    316 https://doi.org/10.1038/leu.2013.77
    317 rdf:type schema:CreativeWork
    318 sg:pub.10.1038/leu.2016.350 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034557565
    319 https://doi.org/10.1038/leu.2016.350
    320 rdf:type schema:CreativeWork
    321 sg:pub.10.1038/ncb1571 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041654071
    322 https://doi.org/10.1038/ncb1571
    323 rdf:type schema:CreativeWork
    324 sg:pub.10.1038/ncb3380 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012428907
    325 https://doi.org/10.1038/ncb3380
    326 rdf:type schema:CreativeWork
    327 sg:pub.10.1038/ncomms14382 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083733644
    328 https://doi.org/10.1038/ncomms14382
    329 rdf:type schema:CreativeWork
    330 sg:pub.10.1038/s41375-019-0377-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111616404
    331 https://doi.org/10.1038/s41375-019-0377-0
    332 rdf:type schema:CreativeWork
    333 sg:pub.10.1038/s41568-020-0262-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1127544291
    334 https://doi.org/10.1038/s41568-020-0262-1
    335 rdf:type schema:CreativeWork
    336 sg:pub.10.1186/s13059-014-0550-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015222646
    337 https://doi.org/10.1186/s13059-014-0550-8
    338 rdf:type schema:CreativeWork
    339 grid-institutes:grid.10392.39 schema:alternateName Department of Hematology, Oncology, Clinical Immunology, University of Tübingen, Tübingen, Germany
    340 schema:name Department of Hematology, Oncology, Clinical Immunology, University of Tübingen, Tübingen, Germany
    341 rdf:type schema:Organization
    342 grid-institutes:grid.10423.34 schema:alternateName Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
    343 Department of Human Genetics, Hannover Medical School, Hannover, Germany
    344 Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany
    345 Institute of Pathology, Hannover Medical School, Hannover, Germany
    346 Research Core Unit Genomics, Hannover Medical School, Hannover, Germany
    347 schema:name Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
    348 Department of Human Genetics, Hannover Medical School, Hannover, Germany
    349 Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany
    350 Institute of Pathology, Hannover Medical School, Hannover, Germany
    351 Research Core Unit Genomics, Hannover Medical School, Hannover, Germany
    352 rdf:type schema:Organization
    353 grid-institutes:grid.16821.3c schema:alternateName National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    354 schema:name Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
    355 National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    356 rdf:type schema:Organization
    357 grid-institutes:grid.412536.7 schema:alternateName Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, and Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
    358 schema:name Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
    359 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, and Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
    360 rdf:type schema:Organization
    361 grid-institutes:grid.412793.a schema:alternateName Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    362 schema:name Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    363 rdf:type schema:Organization
    364 grid-institutes:grid.459910.0 schema:alternateName Department of Hematology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    365 schema:name Department of Hematology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    366 rdf:type schema:Organization
    367 grid-institutes:grid.488549.c schema:alternateName University Children’s Hospital, Department of General Pediatrics and Pediatric Hematology and Oncology, Tübingen, Germany
    368 schema:name University Children’s Hospital, Department of General Pediatrics and Pediatric Hematology and Oncology, Tübingen, Germany
    369 rdf:type schema:Organization
    370 grid-institutes:grid.5718.b schema:alternateName AML Diagnostic Laboratory, Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany
    371 schema:name AML Diagnostic Laboratory, Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany
    372 rdf:type schema:Organization
     




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


    ...