BCR/ABL Expression of Myeloid Progenitors Increases β1-Integrin Mediated Adhesion to Stromal Cells

Fernando A Fierro, Anna Taubenberger, Pierre Henri Puech, Gerhard Ehninger, Martin Bornhauser, Daniel J. Muller, Thomas Illmer

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The expression of the fusion protein BCR/ABL is a hallmark of chronic myeloid leukemia. BCR/ABL is a constitutively active tyrosine kinase influencing cell proliferation, apoptosis, and differentiation. To what extent and by which mechanism BCR/ABL affects the adhesion of leukemic cells to bone marrow stromal cells (BMSC) is controversial. To characterize adhesion of BCR/ABL-transformed 32D cells (32D-BCR/ABL) to the BMSC line M2-10B4, we used washing assays and single-cell force spectroscopy (SCFS). Compared to control 32D cells (32D-V), 32D-BCR/ABL developed threefold higher adhesion forces. This enhanced cell adhesion could be reduced to control levels after specifically inhibiting the activity of the tyrosine kinase BCR/ABL using imatinib mesylate (IM). SCFS showed that the adhesion forces of 32D-BCR/ABL were strongest to fibronectin and collagen type I, suggesting that β1-integrin has a major role in mediating the adhesion of leukemic cells to BMSC. Indeed, the β1-integrin blocking antibody Ha2/5 abrogated the attachment of 32D-V and 32D-BCR/ABL cells to BMSC. Although 32D-BCR/ABL cells show significantly increased β1-integrin expression, no significant difference of β1-integrin mRNA levels could be detected, indicating a post-transcriptional regulation of β1-comprising integrin heterodimers by BCR/ABL. The data presented here argue that the interaction of β1-integrin and extracellular matrix components is functionally important in leukemic cells expressing high-levels of BCR/ABL, and could provide a rationale for the development of optimized targeted therapies.

Original languageEnglish (US)
Pages (from-to)1082-1093
Number of pages12
JournalJournal of Molecular Biology
Volume377
Issue number4
DOIs
StatePublished - Apr 4 2008
Externally publishedYes

    Fingerprint

Keywords

  • atomic force microscopy
  • BCR/ABL
  • bone marrow stromal cells
  • cell adhesion
  • chronic myeloid leukemia

ASJC Scopus subject areas

  • Virology

Cite this

Fierro, F. A., Taubenberger, A., Puech, P. H., Ehninger, G., Bornhauser, M., Muller, D. J., & Illmer, T. (2008). BCR/ABL Expression of Myeloid Progenitors Increases β1-Integrin Mediated Adhesion to Stromal Cells. Journal of Molecular Biology, 377(4), 1082-1093. https://doi.org/10.1016/j.jmb.2008.01.085