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Oncogene. 2002 May 9;21(20):3225-31.

BCR/ABL P190 transgenic mice develop leukemia in the absence of Crkl.

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1
Section of Molecular Carcinogenesis, Division of Hematology/Oncology, Ms #54, Childrens Hospital of Los Angeles Research Institute, and the Keck School of Medicine-University of Southern California, Los Angeles, CA 90027, USA.

Abstract

The Bcr/Abl fusion protein directly causes chronic myelogenous leukemia and Philadelphia-chromosome positive acute lymphoblastic leukemia. Multiple independent studies have implicated Crkl, a small adapter protein, in transduction of oncogenic signals of Bcr/Abl and Crkl tyrosine-phosphorylation is used as a diagnostic tool for Philadelphia-positive leukemia. To evaluate the contribution of Crkl to this type of leukemia, we generated mutant mice that lack Crkl expression. We found that the overall survival of P190 BCR/ABL crkl-/- mice was comparable to that of genetically matched P190 BCR/ABL crkl +/+ mice. Both genotypes developed lymphoid lineage leukemia/lymphoma. Western blot analysis of -/- and +/+ lymphomas showed that the related Crk protein was tyrosine phosphorylated and could be found complexed with Bcr-Abl P190. These data indicate that possible therapeutic approaches that target Crkl may be complicated by the presence of pathways that compensate for lack of Crkl function.

PMID:
12082638
DOI:
10.1038/sj.onc.1205452
[Indexed for MEDLINE]
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