A specific need for CRKL in p210BCR-ABL-induced transformation of mouse hematopoietic progenitors

Cancer Res. 2010 Sep 15;70(18):7325-35. doi: 10.1158/0008-5472.CAN-10-0607. Epub 2010 Aug 31.


CRKL (CRK-like) is an adapter protein predominantly phosphorylated in cells that express the tyrosine kinase p210(BCR-ABL), the fusion product of a (9;22) chromosomal translocation causative for chronic myeloid leukemia. It has been unclear, however, whether CRKL plays a functional role in p210(BCR-ABL) transformation. Here, we show that CRKL is required for p210(BCR-ABL) to support interleukin-3-independent growth of myeloid progenitor cells and long-term outgrowth of B-lymphoid cells from fetal liver-derived hematopoietic progenitor cells. Furthermore, a synthetic phosphotyrosyl peptide that binds to the CRKL SH2 domain with high affinity blocks association of endogenous CRKL with the p210(BCR-ABL) complex and reduces c-MYC levels in K562 human leukemic cells as well as in mouse hematopoietic cells transformed by p210(BCR-ABL) or the imatinib-resistant mutant T315I. These results indicate that the function of CRKL as an adapter protein is essential for p210(BCR-ABL)-induced transformation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Growth Processes / physiology
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Fusion Proteins, bcr-abl / metabolism*
  • Hematopoietic Stem Cells / metabolism*
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Interleukin-3 / pharmacology
  • K562 Cells
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • STAT5 Transcription Factor / metabolism
  • bcl-X Protein / metabolism


  • Adaptor Proteins, Signal Transducing
  • CRKL protein
  • Interleukin-3
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • STAT5 Transcription Factor
  • bcl-X Protein
  • Fusion Proteins, bcr-abl