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

Oncogene. 2002 May 9;21(20):3225-31. doi: 10.1038/sj.onc.1205452.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Transformation, Neoplastic / genetics
  • Drug Design
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / physiology*
  • Genotype
  • Humans
  • Leukemia, Experimental / genetics*
  • Lymphocytes / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Neoplastic Stem Cells / pathology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-crk
  • Signal Transduction / physiology


  • Antineoplastic Agents
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • Fusion Proteins, bcr-abl