| First Author | Wu QL | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 13 | Pages | 3031-9 |
| PubMed ID | 19179304 | Mgi Jnum | J:147170 |
| Mgi Id | MGI:3839518 | Doi | 10.1182/blood-2008-06-163303 |
| Citation | Wu QL, et al. (2009) 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 |
| abstractText | 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. |
