c-CBL is not required for leukemia induction by Bcr-Abl in mice

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.

DOI: 10.1038/sj.onc.1206892

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@article{Dinulescu2003cCBLIN, title={c-CBL is not required for leukemia induction by Bcr-Abl in mice}, author={Daniela M. Dinulescu and Lisa Wood and Lei Shen and Marc M. Loriaux and Christopher Corless and Alec W. Gross and Ruibao Ren and Michael W. N. Deininger and Brian J. Druker}, journal={Oncogene}, year={2003}, volume={22}, pages={8852-8860} }