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

Oncogene volume 21, pages 3225–3231 (2002)Cite this article

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.

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Acknowledgements

Crkl (clone 2-2) and AbI (clone 3F12) monoclonal antibodies were a kind gift of Dr Ravi Salgia (Dana-Farber Cancer Institute, Boston, MA, USA). We thank Suparna Mishra for helping us with the pathological analysis. This work was supported by Public Health Service grants CA 50248 and CA 90321 (N Heisterkamp) and grants from the T.J. Martell Foundation (to N. Heisterkamp and J. Groffen).

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  1. Ron de Jong

    Present address: Idun Pharmaceuticals, La Jolla, CA

Authors and Affiliations

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

    Bianca Hemmeryckx, Anja Reichert, Meguru Watanabe, Ron de Jong, John Groffen & Nora Heisterkamp

  2. Department of Pathology, Childrens Hospital of Los Angeles Research Institute, and the Keck School of Medicine of the University of Southern California, 4650 Sunset Boulevard, Los Angeles, 90027, California CA, USA

    Vesa Kaartinen & Paul K Pattengale

Authors
  1. Bianca Hemmeryckx
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  2. Anja Reichert
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Correspondence to Nora Heisterkamp.

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Hemmeryckx, B., Reichert, A., Watanabe, M. et al. BCR/ABL P190 transgenic mice develop leukemia in the absence of Crkl. Oncogene 21, 3225–3231 (2002). https://doi.org/10.1038/sj.onc.1205452

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