Dysregulation of Frizzled 6 is a critical component of B-cell leukemogenesis in a mouse model of chronic lymphocytic leukemia.
Blood
; 113(13): 3031-9, 2009 Mar 26.
Article
em En
| MEDLINE
| ID: mdl-19179304
ABSTRACT
Wnt/Fzd signaling is known to play a key role in development, tissue-specific stem-cell maintenance, and tumorigenesis, particularly through the canonical pathway involving stabilization of beta-catenin. We have previously shown that Fzd9(-/-) mice have a deficiency in pre-B cells at a stage when self-renewing division is occurring in preference to further differentiation, before light chain immunoglobulin recombination. To determine whether pathologic usurpation of this pathway plays a role in B-cell leukemogenesis, we examined the expression of Wnt/Fzd pathway genes in the Emu-TCL1 mouse model of chronic lymphocytic leukemia. We find that, in the course of leukemogenesis, the expression of Wnt16, Wnt10alpha, Fzd1, and most dramatically, Fzd6, is progressively up-regulated in the transformed CD5(+) B cells of these mice, as are beta-catenin protein levels. Elimination of Fzd6 expression by crossing into Fzd6(-/-) mice significantly delays development of chronic lymphocytic leukemia in this model. Our findings suggest that the self-renewal signals mediated by Wnt/Fzd that are enlisted during B-cell development may be pathologically reactivated in the neoplastic transformation of mature B cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Linfocítica Crônica de Células B
/
Transformação Celular Neoplásica
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Receptores Acoplados a Proteínas G
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Modelos Animais de Doenças
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Receptores Frizzled
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos