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

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

Author information

  • 1Ben May Department for Cancer Research, Committees on Developmental Biology, Genetics, Cancer Biology, and Cell Physiology, University of Chicago, Chicago, IL 60637, USA.

Abstract

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.

©2010 AACR.

PMID:
20807813
[PubMed - indexed for MEDLINE]
PMCID:
PMC2940946
Free PMC Article
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