The chemokine interleukin-8 and the surface activation protein CD69 are markers for Bcr–Abl activity in chronic myeloid leukemia

Hantschel, Oliver; Gstoettenbauer, Agnes; Colinge, Jacques; Kaupe, Ines; Bilban, Martin; Burkard, Thomas R.; Valent, Peter; Superti-Furga, Giulio

doi:10.1016/j.molonc.2008.07.003

« Previous Next »Molecular Oncology
Volume 2, Issue 3 , Pages 272-281, October 2008

The chemokine interleukin-8 and the surface activation protein CD69 are markers for Bcr–Abl activity in chronic myeloid leukemia

Oliver Hantschel
- Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 19, 1090 Vienna, Austria
- O.H. and A.G. contributed equally to this study.
Agnes Gstoettenbauer
- Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 19, 1090 Vienna, Austria
- O.H. and A.G. contributed equally to this study.
Jacques Colinge
- Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 19, 1090 Vienna, Austria
Ines Kaupe
- Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 19, 1090 Vienna, Austria
Martin Bilban
- Department of Laboratory Medicine, Medical University of Vienna and Ludwig Boltzmann Institute for Clinical and Experimental Oncology, Währinger Gürtel 18–20, 1090 Vienna, Austria
Thomas R. Burkard
- Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 19, 1090 Vienna, Austria
Peter Valent
- Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
Giulio Superti-Furga
- Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 19, 1090 Vienna, Austria
- Corresponding author. Tel.: +43 1 40160 70001; fax: +43 1 40160 970000.

Received 3 June 2008; received in revised form 15 July 2008; accepted 16 July 2008. published online 11 August 2008.

Abstract

We have identified differentially regulated genes in chronic myeloid leukemia (CML) cells upon short treatment with the broad-spectrum Bcr–Abl inhibitor dasatinib. The highly specific Bcr–Abl inhibitor nilotinib caused a very similar gene expression signature, validating the identified differentially regulated genes as a read-out of Bcr–Abl activity and implying that Bcr–Abl is the functionally central target of dasatinib in CML cells. Among the strongest downregulated genes, we have further validated the activation marker CD69 and the chemokine interleukin (IL)-8. Expression of both proteins is upregulated upon Bcr–Abl expression and inhibited by dasatinib and nilotinib. IL-8 may thus be a useful marker for the monitoring of CML inhibitor efficacy and play a potential pathophysiological role in CML.

Keywords: Bcr–Abl, Chronic myeloid leukemia, Tyrosine kinase inhibitor, Biomarker, Imatinib