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

Ji Heui Seo, Lisa J. Wood, Anupriya Agarwal, Thomas O'Hare, Collin R. Elsea, Ian J. Griswold, Michael W.N. Deininger, Akira Imamoto, Brian J. Druker

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

CRKL (CRK-like) is an adapter protein predominantly phosphorylated in cells that express the tyrosine kinase p210BCR-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 p210BCR-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 p210BCR-ABL complex and reduces c-MYC levels in K562 human leukemic cells as well as in mouse hematopoietic cells transformed by p210BCR-ABL or the imatinib-resistant mutant T315I. These results indicate that the function of CRKL as an adapter protein is essential for p210BCR-ABL - induced transformation.

Original languageEnglish (US)
Pages (from-to)7325-7335
Number of pages11
JournalCancer Research
Volume70
Issue number18
DOIs
StatePublished - Sep 15 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Seo, J. H., Wood, L. J., Agarwal, A., O'Hare, T., Elsea, C. R., Griswold, I. J., Deininger, M. W. N., Imamoto, A., & Druker, B. J. (2010). A specific need for CRKL in p210BCR-ABL - Induced transformation of mouse hematopoietic progenitors. Cancer Research, 70(18), 7325-7335. https://doi.org/10.1158/0008-5472.CAN-10-0607