Leukemic potential of doubly mutant Nf1 and Wv hematopoietic cells

David A. Ingram, Mary Jo Wenning, Kevin Shannon, D. Wade Clapp

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 p21ras, 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.

Original languageEnglish
Pages (from-to)1984-1986
Number of pages3
JournalBlood
Volume101
Issue number5
DOIs
StatePublished - Mar 1 2003

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Juvenile Myelomonocytic Leukemia
Leukemia
Genes
GTPase-Activating Proteins
Pediatrics
Stem Cell Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Hematopoietic Stem Cells
Stem cells
Tumor Suppressor Genes
Tumors
Embryonic Structures
Alleles
Mutation

ASJC Scopus subject areas

  • Hematology

Cite this

Leukemic potential of doubly mutant Nf1 and Wv hematopoietic cells. / Ingram, David A.; Wenning, Mary Jo; Shannon, Kevin; Clapp, D. Wade.

In: Blood, Vol. 101, No. 5, 01.03.2003, p. 1984-1986.

Research output: Contribution to journalArticle

Ingram, David A. ; Wenning, Mary Jo ; Shannon, Kevin ; Clapp, D. Wade. / Leukemic potential of doubly mutant Nf1 and Wv hematopoietic cells. In: Blood. 2003 ; Vol. 101, No. 5. pp. 1984-1986.
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