Quantitative effects of Nf1 inactivation on in vivo hematopoiesis

Youyan Zhang, Brigit R. Taylor, Kevin Shannon, D. Clapp

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The NF1 tumor-suppressor gene is frequently inactivated in juvenile myelomonocytic leukemia, and Nf1 mutant mice model this myeloproliferative disorder (MPD). Competitive repopulation assays were performed to quantify the proliferative advantage of Nf1-/-hematopoietic cells in vivo. Nf1 mutant stem cells demonstrated a growth advantage that was greatest in myeloid lineage cells and least pronounced in Tlymphocytes. Surprisingly, although low numbers of Nf1-deficient cells consistently out-competed wild-type cells, levels of chimerism were stable over months of observation, and MPD was not observed unless threshold numbers of mutant cells were injected. These data showing that normal competitor cells can strongly modulate the growth of mutant populations in vivo have general implications for modeling cancer in the mouse. In particular, strains in which cancer-associated mutations are expressed in fields of target cells may not accurately model early events in tumorigenesis because they eliminate the requirement for a mutant clone to outcompete resident normal cells.

Original languageEnglish
Pages (from-to)709-715
Number of pages7
JournalJournal of Clinical Investigation
Volume108
Issue number5
DOIs
StatePublished - 2001

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Hematopoiesis
Myeloproliferative Disorders
Juvenile Myelomonocytic Leukemia
Chimerism
Population Growth
Myeloid Cells
Tumor Suppressor Genes
Neoplasms
Carcinogenesis
Stem Cells
Clone Cells
Cell Count
Observation
Mutation
Growth

ASJC Scopus subject areas

  • Medicine(all)

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Quantitative effects of Nf1 inactivation on in vivo hematopoiesis. / Zhang, Youyan; Taylor, Brigit R.; Shannon, Kevin; Clapp, D.

In: Journal of Clinical Investigation, Vol. 108, No. 5, 2001, p. 709-715.

Research output: Contribution to journalArticle

Zhang, Youyan ; Taylor, Brigit R. ; Shannon, Kevin ; Clapp, D. / Quantitative effects of Nf1 inactivation on in vivo hematopoiesis. In: Journal of Clinical Investigation. 2001 ; Vol. 108, No. 5. pp. 709-715.
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