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

Daniela M. Dinulescu, Lisa J. Wood, Lei Shen, Marc Loriaux, Christopher L. Corless, Alec W. Gross, Ruibao Ren, Michael W.N. Deininger, Brian J. Druker

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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 languageEnglish (US)
Pages (from-to)8852-8860
Number of pages9
Issue number55
StatePublished - Dec 4 2003


  • Bcr-Abl
  • CML
  • Leukemia
  • c-Cbl

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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