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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2003-2-13
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pubmed:abstractText |
The development of molecularly targeted treatments of adult leukemias warrants investigation of these targets in similar pediatric leukemias. The NF1 tumor suppressor gene, which encodes a GTPase activating protein for p21(ras), is frequently inactivated in juvenile myelomonocytic leukemia (JMML). Other patients with JMML acquire activating RAS gene mutations. Recipient mice reconstituted with Nf1-/- fetal hematopoietic cells develop a myeloproliferative disease (MPD) that models the human disease. JMML arises from clonal expansion of a hematopoietic stem cell, and JMML cells and murine Nf1-/- hematopoietic cells are hypersensitive to granulocyte macrophage-colony stimulating factor and KitL, the ligand for c-kit. We generated embryos doubly mutant for the Wv allele of c-kit and Nf1 to ask if reduction of c-kit activity would delay or prevent the development of MPD. Despite a reduction in c-kit activity to approximately 10% of wild-type levels, Nf1-/-;Wv/Wv cells induced MPD in recipient mice.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1984-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12393498-Alleles,
pubmed-meshheading:12393498-Animals,
pubmed-meshheading:12393498-Cell Transformation, Neoplastic,
pubmed-meshheading:12393498-Colony-Forming Units Assay,
pubmed-meshheading:12393498-Crosses, Genetic,
pubmed-meshheading:12393498-Disease Models, Animal,
pubmed-meshheading:12393498-Gene Targeting,
pubmed-meshheading:12393498-Genes, Neurofibromatosis 1,
pubmed-meshheading:12393498-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:12393498-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:12393498-Interleukin-1,
pubmed-meshheading:12393498-Interleukin-3,
pubmed-meshheading:12393498-Leukemia, Myelomonocytic, Acute,
pubmed-meshheading:12393498-Liver,
pubmed-meshheading:12393498-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:12393498-Mice,
pubmed-meshheading:12393498-Mice, Inbred C57BL,
pubmed-meshheading:12393498-Mice, Mutant Strains,
pubmed-meshheading:12393498-Myeloproliferative Disorders,
pubmed-meshheading:12393498-Neurofibromin 1,
pubmed-meshheading:12393498-Proto-Oncogene Proteins c-kit,
pubmed-meshheading:12393498-Radiation Chimera,
pubmed-meshheading:12393498-Recombinant Proteins,
pubmed-meshheading:12393498-Stem Cell Factor
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pubmed:year |
2003
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pubmed:articleTitle |
Leukemic potential of doubly mutant Nf1 and Wv hematopoietic cells.
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pubmed:affiliation |
Indiana University School of Medicine, Herman B. Wells Center for Pediatric Research, Department of Microbiology/Immunology, Indianapolis, IN 46202, USA. dingram@iupui.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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