FLT3 mutations in acute myeloid leukemia cell lines View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-01

AUTHORS

H Quentmeier, J Reinhardt, M Zaborski, H G Drexler

ABSTRACT

Internal tandem duplications (ITD) and D835 point mutations of the receptor tyrosine kinase (RTK) FLT3 are found in a high proportion of cases with acute myeloid leukemia (AML). These genetic aberrations may lead to the constitutive activation of the receptor, thus providing the molecular basis for a persisting growth stimulus. We have screened 69 AML-derived cell lines for FLT3 mutations. Four of these cell lines showed ITD of the FLT3 gene, none carried a D835 point mutation. Two cell lines (MUTZ-11 and MV4-11) expressed exclusively the mutated allele, the other two cell lines (MOLM-13 and PL-21) displayed a mutated and the wild-type version of the gene. Although mutationally activated FLT3 is supposed to substitute for the stimulatory signal of a growth factor, one of these cell lines (MUTZ-11) was strictly cytokine-dependent. FLT3 transcripts were found in all four cell lines, but the constitutively phosphorylated receptor protein was clearly detectable only in cell line MV4-11, possibly explaining why MUTZ-11 cells were growth-factor dependent. Thus, not all FLT3 ITD-positive cells express high levels of the active receptor protein, a finding that might be of relevance for a possible future application of a kinase inhibitor as therapeutic agent. It had been described that STAT-5 phosphorylation was part of the FLT3 signalling chain and that STAT-5 molecules were constitutively phosphorylated in FLT3 ITD-positive cells. Although we observed the constitutive phosphorylation of STAT-5 molecules in FLT3-mutant cells, FLT3 ligand (FL) did not induce STAT-5 phosphorylation in FLT3 wild-type cells. These results suggest that the signalling mechanisms of the mutated FL receptor differ at least to some extent from those conferred by wild-type FLT3. In conclusion, (1) not all cells with FLT3 ITD express significant amounts of the mutated receptor protein; (2) signals downstream from wild-type and mutant FLT3 receptors are not 100% identical; and (3) MV4-11 represents a model cell line for FLT3 ITD signalling. More... »

PAGES

2402740

Journal

TITLE

Leukemia

ISSUE

1

VOLUME

17

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.leu.2402740

DOI

http://dx.doi.org/10.1038/sj.leu.2402740

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041582176

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12529668


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/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Acute Disease", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Base Sequence", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Blotting, Western", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Transformation, Neoplastic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA-Binding Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Expression Regulation, Leukemic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Leukemia, Myeloid", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Milk Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Molecular Sequence Data", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Phosphorylation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Phosphotyrosine", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Point Mutation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Proto-Oncogene Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptor Protein-Tyrosine Kinases", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptors, Cell Surface", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "STAT5 Transcription Factor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Signal Transduction", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Tandem Repeat Sequences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Thymidine", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Trans-Activators", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Tumor Cells, Cultured", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "fms-Like Tyrosine Kinase 3", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Leibniz Institute DSMZ \u2013 German Collection of Microorganisms and Cell Cultures", 
          "id": "https://www.grid.ac/institutes/grid.420081.f", 
          "name": [
            "DSMZ \u2013 German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Quentmeier", 
        "givenName": "H", 
        "id": "sg:person.01230641077.20", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01230641077.20"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Leibniz Institute DSMZ \u2013 German Collection of Microorganisms and Cell Cultures", 
          "id": "https://www.grid.ac/institutes/grid.420081.f", 
          "name": [
            "DSMZ \u2013 German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Reinhardt", 
        "givenName": "J", 
        "id": "sg:person.01172401070.13", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01172401070.13"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Leibniz Institute DSMZ \u2013 German Collection of Microorganisms and Cell Cultures", 
          "id": "https://www.grid.ac/institutes/grid.420081.f", 
          "name": [
            "DSMZ \u2013 German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zaborski", 
        "givenName": "M", 
        "id": "sg:person.01353530774.21", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01353530774.21"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Leibniz Institute DSMZ \u2013 German Collection of Microorganisms and Cell Cultures", 
          "id": "https://www.grid.ac/institutes/grid.420081.f", 
          "name": [
            "DSMZ \u2013 German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Drexler", 
        "givenName": "H G", 
        "id": "sg:person.012672532002.99", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012672532002.99"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1046/j.0007-1048.2001.03294.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000705220"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.271.33.20075", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001281667"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2401130", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002471707", 
          "https://doi.org/10.1038/sj.leu.2401130"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2401130", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002471707", 
          "https://doi.org/10.1038/sj.leu.2401130"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1203354", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004579728", 
          "https://doi.org/10.1038/sj.onc.1203354"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1203354", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004579728", 
          "https://doi.org/10.1038/sj.onc.1203354"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1084/jem.192.5.719", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010425859"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood.v97.8.2434", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014730117"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2400756", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014805578", 
          "https://doi.org/10.1038/sj.leu.2400756"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2400756", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014805578", 
          "https://doi.org/10.1038/sj.leu.2400756"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood.v98.3.885", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019011103"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2141.2000.01831.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021586389"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2402199", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024534677", 
          "https://doi.org/10.1038/sj.leu.2402199"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2402199", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024534677", 
          "https://doi.org/10.1038/sj.leu.2402199"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2400812", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025757807", 
          "https://doi.org/10.1038/sj.leu.2400812"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2400812", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025757807", 
          "https://doi.org/10.1038/sj.leu.2400812"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2402367", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028181477", 
          "https://doi.org/10.1038/sj.leu.2402367"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2402367", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028181477", 
          "https://doi.org/10.1038/sj.leu.2402367"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2141.2001.02821.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030394496"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood.v97.1.89", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034401911"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2401905", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048114071", 
          "https://doi.org/10.1038/sj.leu.2401905"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2401905", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048114071", 
          "https://doi.org/10.1038/sj.leu.2401905"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2141.2001.02850.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049247071"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2401731", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052319870", 
          "https://doi.org/10.1038/sj.leu.2401731"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2401731", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052319870", 
          "https://doi.org/10.1038/sj.leu.2401731"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2402317", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053044350", 
          "https://doi.org/10.1038/sj.leu.2402317"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.leu.2402317", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053044350", 
          "https://doi.org/10.1038/sj.leu.2402317"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3892/ijo.14.4.765", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071510997"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074362860", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074542236", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074731723", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074889457", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1076061311", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082446965", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082860419", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082888284", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082888287", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082974515", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083009621", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2003-01", 
    "datePublishedReg": "2003-01-01", 
    "description": "Internal tandem duplications (ITD) and D835 point mutations of the receptor tyrosine kinase (RTK) FLT3 are found in a high proportion of cases with acute myeloid leukemia (AML). These genetic aberrations may lead to the constitutive activation of the receptor, thus providing the molecular basis for a persisting growth stimulus. We have screened 69 AML-derived cell lines for FLT3 mutations. Four of these cell lines showed ITD of the FLT3 gene, none carried a D835 point mutation. Two cell lines (MUTZ-11 and MV4-11) expressed exclusively the mutated allele, the other two cell lines (MOLM-13 and PL-21) displayed a mutated and the wild-type version of the gene. Although mutationally activated FLT3 is supposed to substitute for the stimulatory signal of a growth factor, one of these cell lines (MUTZ-11) was strictly cytokine-dependent. FLT3 transcripts were found in all four cell lines, but the constitutively phosphorylated receptor protein was clearly detectable only in cell line MV4-11, possibly explaining why MUTZ-11 cells were growth-factor dependent. Thus, not all FLT3 ITD-positive cells express high levels of the active receptor protein, a finding that might be of relevance for a possible future application of a kinase inhibitor as therapeutic agent. It had been described that STAT-5 phosphorylation was part of the FLT3 signalling chain and that STAT-5 molecules were constitutively phosphorylated in FLT3 ITD-positive cells. Although we observed the constitutive phosphorylation of STAT-5 molecules in FLT3-mutant cells, FLT3 ligand (FL) did not induce STAT-5 phosphorylation in FLT3 wild-type cells. These results suggest that the signalling mechanisms of the mutated FL receptor differ at least to some extent from those conferred by wild-type FLT3. In conclusion, (1) not all cells with FLT3 ITD express significant amounts of the mutated receptor protein; (2) signals downstream from wild-type and mutant FLT3 receptors are not 100% identical; and (3) MV4-11 represents a model cell line for FLT3 ITD signalling.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/sj.leu.2402740", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1097065", 
        "issn": [
          "0887-6924", 
          "1476-5551"
        ], 
        "name": "Leukemia", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "17"
      }
    ], 
    "name": "FLT3 mutations in acute myeloid leukemia cell lines", 
    "pagination": "2402740", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "c615615e060e4af13a6c4fded782a42a7644c621805eab305f4f3c401d688020"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "12529668"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "8704895"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/sj.leu.2402740"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1041582176"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/sj.leu.2402740", 
      "https://app.dimensions.ai/details/publication/pub.1041582176"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T12:07", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000360_0000000360/records_118344_00000001.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://www.nature.com/articles/2402740"
  }
]
 

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/sj.leu.2402740'

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/sj.leu.2402740'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.leu.2402740'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.leu.2402740'


 

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

270 TRIPLES      21 PREDICATES      82 URIs      44 LITERALS      32 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/sj.leu.2402740 schema:about N1543ec9ca86142f18d3f0c2a2adbee4e
2 N1f28b56c79254372860002a262ecae9c
3 N308776d26f674b72aabe855dbd590f4f
4 N33f778254c5145a6b1d54d42aea348f1
5 N3610c0e76afe4f8a811a4f8682b99e4b
6 N38fe121fa08842b6a60f5695e05c9569
7 N7f232de244344678ae96ca5a1f7202ec
8 N7f64d05254794db494a687a53e99ae5a
9 N96eda78cf7b041df817453b4e478d95c
10 Na0d9ecf812a84bb089848205df1e5720
11 Na1f50917afe040408c3ccfc72da8e68f
12 Na33290a9e33e4a4ba3427957fdc484c6
13 Na489c8f78a3d49a6a54005e0e26fc078
14 Nae7c7de5d58042f6bca22aaa107204e4
15 Nba6a3b2eb85e4e37a133aec610465666
16 Nc1b5867bae1642839a855c5dc69def3a
17 Ncea085a383944f7b9bfee2ebeaf9059b
18 Nd3321bf2868c45488b2c0aff68d1c8b7
19 Nda3aa21ca6d947a49bd2af81414fbaae
20 Ndaf704ac5b854bea9cf7a42bc12d75fa
21 Ne732132f02244467b7362aa0c7113f90
22 Nf299750c2a7047d0b91dcbedd05e76b5
23 Nf52bf60306df4a04b2dc6b7adb3c00dc
24 anzsrc-for:06
25 anzsrc-for:0601
26 schema:author N234cdd5a313e4538a60ad4cf28a20a15
27 schema:citation sg:pub.10.1038/sj.leu.2400756
28 sg:pub.10.1038/sj.leu.2400812
29 sg:pub.10.1038/sj.leu.2401130
30 sg:pub.10.1038/sj.leu.2401731
31 sg:pub.10.1038/sj.leu.2401905
32 sg:pub.10.1038/sj.leu.2402199
33 sg:pub.10.1038/sj.leu.2402317
34 sg:pub.10.1038/sj.leu.2402367
35 sg:pub.10.1038/sj.onc.1203354
36 https://app.dimensions.ai/details/publication/pub.1074362860
37 https://app.dimensions.ai/details/publication/pub.1074542236
38 https://app.dimensions.ai/details/publication/pub.1074731723
39 https://app.dimensions.ai/details/publication/pub.1074889457
40 https://app.dimensions.ai/details/publication/pub.1076061311
41 https://app.dimensions.ai/details/publication/pub.1082446965
42 https://app.dimensions.ai/details/publication/pub.1082860419
43 https://app.dimensions.ai/details/publication/pub.1082888284
44 https://app.dimensions.ai/details/publication/pub.1082888287
45 https://app.dimensions.ai/details/publication/pub.1082974515
46 https://app.dimensions.ai/details/publication/pub.1083009621
47 https://doi.org/10.1046/j.0007-1048.2001.03294.x
48 https://doi.org/10.1046/j.1365-2141.2000.01831.x
49 https://doi.org/10.1046/j.1365-2141.2001.02821.x
50 https://doi.org/10.1046/j.1365-2141.2001.02850.x
51 https://doi.org/10.1074/jbc.271.33.20075
52 https://doi.org/10.1084/jem.192.5.719
53 https://doi.org/10.1182/blood.v97.1.89
54 https://doi.org/10.1182/blood.v97.8.2434
55 https://doi.org/10.1182/blood.v98.3.885
56 https://doi.org/10.3892/ijo.14.4.765
57 schema:datePublished 2003-01
58 schema:datePublishedReg 2003-01-01
59 schema:description Internal tandem duplications (ITD) and D835 point mutations of the receptor tyrosine kinase (RTK) FLT3 are found in a high proportion of cases with acute myeloid leukemia (AML). These genetic aberrations may lead to the constitutive activation of the receptor, thus providing the molecular basis for a persisting growth stimulus. We have screened 69 AML-derived cell lines for FLT3 mutations. Four of these cell lines showed ITD of the FLT3 gene, none carried a D835 point mutation. Two cell lines (MUTZ-11 and MV4-11) expressed exclusively the mutated allele, the other two cell lines (MOLM-13 and PL-21) displayed a mutated and the wild-type version of the gene. Although mutationally activated FLT3 is supposed to substitute for the stimulatory signal of a growth factor, one of these cell lines (MUTZ-11) was strictly cytokine-dependent. FLT3 transcripts were found in all four cell lines, but the constitutively phosphorylated receptor protein was clearly detectable only in cell line MV4-11, possibly explaining why MUTZ-11 cells were growth-factor dependent. Thus, not all FLT3 ITD-positive cells express high levels of the active receptor protein, a finding that might be of relevance for a possible future application of a kinase inhibitor as therapeutic agent. It had been described that STAT-5 phosphorylation was part of the FLT3 signalling chain and that STAT-5 molecules were constitutively phosphorylated in FLT3 ITD-positive cells. Although we observed the constitutive phosphorylation of STAT-5 molecules in FLT3-mutant cells, FLT3 ligand (FL) did not induce STAT-5 phosphorylation in FLT3 wild-type cells. These results suggest that the signalling mechanisms of the mutated FL receptor differ at least to some extent from those conferred by wild-type FLT3. In conclusion, (1) not all cells with FLT3 ITD express significant amounts of the mutated receptor protein; (2) signals downstream from wild-type and mutant FLT3 receptors are not 100% identical; and (3) MV4-11 represents a model cell line for FLT3 ITD signalling.
60 schema:genre research_article
61 schema:inLanguage en
62 schema:isAccessibleForFree true
63 schema:isPartOf N09eb52f579564b179a24e59c96b811c0
64 N34277a3b41ec4246ba83b69df65dae95
65 sg:journal.1097065
66 schema:name FLT3 mutations in acute myeloid leukemia cell lines
67 schema:pagination 2402740
68 schema:productId N27547077022843259802f9b91ef1ba8c
69 N3cf51fc7d6274e49a2294e16e356f0e6
70 Nb94841a74dfa4f8da804160b8667aafb
71 Nbad0ff05e03d4cd2acda8a056761cab7
72 Nd50593e8822b480aa3f87caaa5c71485
73 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041582176
74 https://doi.org/10.1038/sj.leu.2402740
75 schema:sdDatePublished 2019-04-11T12:07
76 schema:sdLicense https://scigraph.springernature.com/explorer/license/
77 schema:sdPublisher N2e6b2e0420db4d1280eca5dfc3ee11df
78 schema:url http://www.nature.com/articles/2402740
79 sgo:license sg:explorer/license/
80 sgo:sdDataset articles
81 rdf:type schema:ScholarlyArticle
82 N09eb52f579564b179a24e59c96b811c0 schema:issueNumber 1
83 rdf:type schema:PublicationIssue
84 N1543ec9ca86142f18d3f0c2a2adbee4e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
85 schema:name Receptor Protein-Tyrosine Kinases
86 rdf:type schema:DefinedTerm
87 N1f28b56c79254372860002a262ecae9c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
88 schema:name Molecular Sequence Data
89 rdf:type schema:DefinedTerm
90 N234cdd5a313e4538a60ad4cf28a20a15 rdf:first sg:person.01230641077.20
91 rdf:rest N617cbd5e48894efa9184c121771a6549
92 N27547077022843259802f9b91ef1ba8c schema:name nlm_unique_id
93 schema:value 8704895
94 rdf:type schema:PropertyValue
95 N2e6b2e0420db4d1280eca5dfc3ee11df schema:name Springer Nature - SN SciGraph project
96 rdf:type schema:Organization
97 N308776d26f674b72aabe855dbd590f4f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
98 schema:name Signal Transduction
99 rdf:type schema:DefinedTerm
100 N33f778254c5145a6b1d54d42aea348f1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
101 schema:name Receptors, Cell Surface
102 rdf:type schema:DefinedTerm
103 N34277a3b41ec4246ba83b69df65dae95 schema:volumeNumber 17
104 rdf:type schema:PublicationVolume
105 N3610c0e76afe4f8a811a4f8682b99e4b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
106 schema:name Tandem Repeat Sequences
107 rdf:type schema:DefinedTerm
108 N38fe121fa08842b6a60f5695e05c9569 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
109 schema:name Milk Proteins
110 rdf:type schema:DefinedTerm
111 N3cf51fc7d6274e49a2294e16e356f0e6 schema:name pubmed_id
112 schema:value 12529668
113 rdf:type schema:PropertyValue
114 N408913eeec074eb29a82a6e2be239c58 rdf:first sg:person.012672532002.99
115 rdf:rest rdf:nil
116 N617cbd5e48894efa9184c121771a6549 rdf:first sg:person.01172401070.13
117 rdf:rest N85ce0f6c4f1142ad9cae4fc0a511a076
118 N7f232de244344678ae96ca5a1f7202ec schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
119 schema:name Tumor Cells, Cultured
120 rdf:type schema:DefinedTerm
121 N7f64d05254794db494a687a53e99ae5a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
122 schema:name Thymidine
123 rdf:type schema:DefinedTerm
124 N85ce0f6c4f1142ad9cae4fc0a511a076 rdf:first sg:person.01353530774.21
125 rdf:rest N408913eeec074eb29a82a6e2be239c58
126 N96eda78cf7b041df817453b4e478d95c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
127 schema:name fms-Like Tyrosine Kinase 3
128 rdf:type schema:DefinedTerm
129 Na0d9ecf812a84bb089848205df1e5720 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name Humans
131 rdf:type schema:DefinedTerm
132 Na1f50917afe040408c3ccfc72da8e68f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
133 schema:name DNA-Binding Proteins
134 rdf:type schema:DefinedTerm
135 Na33290a9e33e4a4ba3427957fdc484c6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
136 schema:name Base Sequence
137 rdf:type schema:DefinedTerm
138 Na489c8f78a3d49a6a54005e0e26fc078 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
139 schema:name Phosphorylation
140 rdf:type schema:DefinedTerm
141 Nae7c7de5d58042f6bca22aaa107204e4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
142 schema:name Trans-Activators
143 rdf:type schema:DefinedTerm
144 Nb94841a74dfa4f8da804160b8667aafb schema:name dimensions_id
145 schema:value pub.1041582176
146 rdf:type schema:PropertyValue
147 Nba6a3b2eb85e4e37a133aec610465666 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Point Mutation
149 rdf:type schema:DefinedTerm
150 Nbad0ff05e03d4cd2acda8a056761cab7 schema:name doi
151 schema:value 10.1038/sj.leu.2402740
152 rdf:type schema:PropertyValue
153 Nc1b5867bae1642839a855c5dc69def3a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
154 schema:name Cell Transformation, Neoplastic
155 rdf:type schema:DefinedTerm
156 Ncea085a383944f7b9bfee2ebeaf9059b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
157 schema:name Leukemia, Myeloid
158 rdf:type schema:DefinedTerm
159 Nd3321bf2868c45488b2c0aff68d1c8b7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
160 schema:name Proto-Oncogene Proteins
161 rdf:type schema:DefinedTerm
162 Nd50593e8822b480aa3f87caaa5c71485 schema:name readcube_id
163 schema:value c615615e060e4af13a6c4fded782a42a7644c621805eab305f4f3c401d688020
164 rdf:type schema:PropertyValue
165 Nda3aa21ca6d947a49bd2af81414fbaae schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
166 schema:name STAT5 Transcription Factor
167 rdf:type schema:DefinedTerm
168 Ndaf704ac5b854bea9cf7a42bc12d75fa schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
169 schema:name Phosphotyrosine
170 rdf:type schema:DefinedTerm
171 Ne732132f02244467b7362aa0c7113f90 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
172 schema:name Gene Expression Regulation, Leukemic
173 rdf:type schema:DefinedTerm
174 Nf299750c2a7047d0b91dcbedd05e76b5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
175 schema:name Blotting, Western
176 rdf:type schema:DefinedTerm
177 Nf52bf60306df4a04b2dc6b7adb3c00dc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
178 schema:name Acute Disease
179 rdf:type schema:DefinedTerm
180 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
181 schema:name Biological Sciences
182 rdf:type schema:DefinedTerm
183 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
184 schema:name Biochemistry and Cell Biology
185 rdf:type schema:DefinedTerm
186 sg:journal.1097065 schema:issn 0887-6924
187 1476-5551
188 schema:name Leukemia
189 rdf:type schema:Periodical
190 sg:person.01172401070.13 schema:affiliation https://www.grid.ac/institutes/grid.420081.f
191 schema:familyName Reinhardt
192 schema:givenName J
193 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01172401070.13
194 rdf:type schema:Person
195 sg:person.01230641077.20 schema:affiliation https://www.grid.ac/institutes/grid.420081.f
196 schema:familyName Quentmeier
197 schema:givenName H
198 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01230641077.20
199 rdf:type schema:Person
200 sg:person.012672532002.99 schema:affiliation https://www.grid.ac/institutes/grid.420081.f
201 schema:familyName Drexler
202 schema:givenName H G
203 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012672532002.99
204 rdf:type schema:Person
205 sg:person.01353530774.21 schema:affiliation https://www.grid.ac/institutes/grid.420081.f
206 schema:familyName Zaborski
207 schema:givenName M
208 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01353530774.21
209 rdf:type schema:Person
210 sg:pub.10.1038/sj.leu.2400756 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014805578
211 https://doi.org/10.1038/sj.leu.2400756
212 rdf:type schema:CreativeWork
213 sg:pub.10.1038/sj.leu.2400812 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025757807
214 https://doi.org/10.1038/sj.leu.2400812
215 rdf:type schema:CreativeWork
216 sg:pub.10.1038/sj.leu.2401130 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002471707
217 https://doi.org/10.1038/sj.leu.2401130
218 rdf:type schema:CreativeWork
219 sg:pub.10.1038/sj.leu.2401731 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052319870
220 https://doi.org/10.1038/sj.leu.2401731
221 rdf:type schema:CreativeWork
222 sg:pub.10.1038/sj.leu.2401905 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048114071
223 https://doi.org/10.1038/sj.leu.2401905
224 rdf:type schema:CreativeWork
225 sg:pub.10.1038/sj.leu.2402199 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024534677
226 https://doi.org/10.1038/sj.leu.2402199
227 rdf:type schema:CreativeWork
228 sg:pub.10.1038/sj.leu.2402317 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053044350
229 https://doi.org/10.1038/sj.leu.2402317
230 rdf:type schema:CreativeWork
231 sg:pub.10.1038/sj.leu.2402367 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028181477
232 https://doi.org/10.1038/sj.leu.2402367
233 rdf:type schema:CreativeWork
234 sg:pub.10.1038/sj.onc.1203354 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004579728
235 https://doi.org/10.1038/sj.onc.1203354
236 rdf:type schema:CreativeWork
237 https://app.dimensions.ai/details/publication/pub.1074362860 schema:CreativeWork
238 https://app.dimensions.ai/details/publication/pub.1074542236 schema:CreativeWork
239 https://app.dimensions.ai/details/publication/pub.1074731723 schema:CreativeWork
240 https://app.dimensions.ai/details/publication/pub.1074889457 schema:CreativeWork
241 https://app.dimensions.ai/details/publication/pub.1076061311 schema:CreativeWork
242 https://app.dimensions.ai/details/publication/pub.1082446965 schema:CreativeWork
243 https://app.dimensions.ai/details/publication/pub.1082860419 schema:CreativeWork
244 https://app.dimensions.ai/details/publication/pub.1082888284 schema:CreativeWork
245 https://app.dimensions.ai/details/publication/pub.1082888287 schema:CreativeWork
246 https://app.dimensions.ai/details/publication/pub.1082974515 schema:CreativeWork
247 https://app.dimensions.ai/details/publication/pub.1083009621 schema:CreativeWork
248 https://doi.org/10.1046/j.0007-1048.2001.03294.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1000705220
249 rdf:type schema:CreativeWork
250 https://doi.org/10.1046/j.1365-2141.2000.01831.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1021586389
251 rdf:type schema:CreativeWork
252 https://doi.org/10.1046/j.1365-2141.2001.02821.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1030394496
253 rdf:type schema:CreativeWork
254 https://doi.org/10.1046/j.1365-2141.2001.02850.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1049247071
255 rdf:type schema:CreativeWork
256 https://doi.org/10.1074/jbc.271.33.20075 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001281667
257 rdf:type schema:CreativeWork
258 https://doi.org/10.1084/jem.192.5.719 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010425859
259 rdf:type schema:CreativeWork
260 https://doi.org/10.1182/blood.v97.1.89 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034401911
261 rdf:type schema:CreativeWork
262 https://doi.org/10.1182/blood.v97.8.2434 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014730117
263 rdf:type schema:CreativeWork
264 https://doi.org/10.1182/blood.v98.3.885 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019011103
265 rdf:type schema:CreativeWork
266 https://doi.org/10.3892/ijo.14.4.765 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071510997
267 rdf:type schema:CreativeWork
268 https://www.grid.ac/institutes/grid.420081.f schema:alternateName Leibniz Institute DSMZ – German Collection of Microorganisms and Cell Cultures
269 schema:name DSMZ – German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany
270 rdf:type schema:Organization
 




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


...