gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Leukemia targeting ligands isolated from phage display peptide libraries

Meeting Abstract

  • corresponding author presenting/speaker Sonja Adebahr - Medizinische Universitätsklinik Freiburg, Deutschland
  • Annett Jahnke - Medizinische Universitätsklinik Freiburg
  • Sebastian Jäger - Medizinische Universitätsklinik Freiburg
  • Tobias Berg - Medizinische Universitätsklinik Freiburg
  • Michael Lübbert - Medizinische Universitätsklinik Freiburg
  • Martin Trepel - Medizinische Universitätsklinik Freiburg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP105

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Adebahr et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background: Ligands specifically binding to leukemia cells may be used to target drugs or gene therapy vectors, resulting in a more effective treatment with less toxic side effects. Little is known about receptors specifically expressed on acute myeloid leukemia cells or ligands thereof. We intended to identify such ligands based on a random phage display peptide selection system. The identification of AML-binding peptide ligands and the subsequent identification of the respective receptors have implications both for basic research and targeting therapies.

Methods and results: We selected random phage display peptide libraries on Kasumi-1 acute myeloid leukemia (AML) cells.One peptide(termed PLD-1)was enriched after three rounds of selection. Phage displaying this peptide bound Kasumi-1 cells almost 100-fold more efficient than control phage and binding could be inhibited competitively by the cognate peptide in a concentration dependent manner. Further binding assays on other AML cells revealed strong PLD-1 phage-binding also to SKNO-1 cells. Both, Kasumi-1 and SKNO-1 cells share a common molecular feature which is the chromosomal translocation 8;21, leading to aberrant expression of the fusion protein AML1-ETO. PLD-1 also strongly bound AML blasts from a patient suffering from AML1-ETO-positive leukemiaas well asU937 cells with forced expression of the AML1-ETO fusion gene, suggesting that the PLD-1 receptor may be upregulated upon AML1-ETO fusion gene expression. Gene expression profiling comparing a panel of PLD1-binding and -non-binding cell lines identified a set of genes encoding potential receptors for the PLD-peptide. Further functional analysis suggested that the integrin α4β1 (VLA4) may be the PLD-1 receptor. Finally we showed that the PLD-1 phage is internalized upon receptor binding suggesting that the PLD-1 receptor-ligand interaction may be exploitable to target drugs or gene therapy vectors to leukemia cells carrying the suitable receptor.

Conclusion: We conclude that the PLD-1 ligand binds to VLA4 on acute myeloid leukemia cells and may be used as a toolachieve targeted therapy, particularly in AML1-ETO positive cells.