1. ¹Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany
2. ²Institute for Molecular Medicine and Cell Research, Freiburg, Germany

Correspondence: Dr M Trepel, Department of Hematology and Oncology, Hugstetter Strasse 55, Freiburg D-79106, Germany. E-mail: trepel@mm11.ukl.uni-freiburg.de

³These two authors contributed equally to this work

Received 26 August 2006; Revised 24 November 2006; Accepted 26 November 2006; Published online 25 January 2007.

Abstract

Ligands specifically binding to leukemia cells may be used for drug targeting, resulting in more effective treatment with less side effects. Little is known about receptors specifically expressed on acute myeloid leukemia (AML) cells or ligands thereof. We selected random phage display peptide libraries on Kasumi-1 AML cells. A peptide with the sequence CPLDIDFYC was enriched. Phage displaying this peptide strongly bound to Kasumi-1 and SKNO-1 cells and binding could be inhibited by the cognate peptide. Both, Kasumi-1 and SKNO-1 cells carry the chromosomal translocation t(8;21), leading to aberrant expression of the fusion protein AML1/ETO. CPLDIDFYC also strongly and specifically bound primary AML1/ETO-positive AML blasts as well as U-937 cells with forced AML1/ETO expression, suggesting that the CPLDIDFYC receptor may be upregulated upon AML1/ETO expression. Gene expression profiling comparing a panel of CPLDIDFYC-binding and CPLDIDFYC-nonbinding cell lines identified a set of potential receptors for the CPLDIDFYC peptide. Further analysis suggested that 41 integrin (VLA-4) is the CPLDIDFYC receptor. Finally, we showed that the CPLDIDFYC-phage is internalized upon receptor binding, suggesting that the CPLDIDFYC-receptor–ligand interaction may be exploitable for targeting drugs or gene therapy vectors to leukemia cells carrying the suitable receptor.