Abstract
Bcr-Abl tyrosine kinase activity is essential for the pathogenesis of chronic myeloid leukemia (CML). A number of Bcr-Abl substrates have been identified, but it is not clear which of these substrates are required for Bcr-Abl to transform cells. The multifunctional protein c-Cbl is one of the most prominently tyrosine-phosphorylated proteins in Bcr-Abl-expressing cells. Using cell lines and mice with homozygous disruption of the c-CBL locus, we investigated the role of this protein for Bcr-Abl-driven transformation. We find that although c-Cbl-/- fibroblast cell lines show a deficit in Bcr-Abl transformation compared to wild-type (Wt) cells, this deficit was less pronounced in C-Cbl-/- B cells derived from murine bone marrow. Most importantly, in a transplantation model of CML, Bcr-Abl was capable of inducing fatal leukemia in mice in the absence of c-Cbl protein. Our results indicate that c-Cbl is dispensable for Bcr-Abl-induced leukemogenesis in mice.
Original language | English (US) |
---|---|
Pages (from-to) | 8852-8860 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 22 |
Issue number | 55 |
DOIs | |
State | Published - Dec 4 2003 |
Keywords
- Bcr-Abl
- CML
- Leukemia
- c-Cbl
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research