Leukemia, 2007-03, Vol.21 (3), p.411-420
2007
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- Autor(en) / Beteiligte
- Titel
- Leukemia targeting ligands isolated from phage display peptide libraries
- Ist Teil von
- Leukemia, 2007-03, Vol.21 (3), p.411-420
- Ort / Verlag
- London: Nature Publishing
- Erscheinungsjahr
- 2007
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 alpha4beta1 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0887-6924eISSN: 1476-5551DOI: 10.1038/sj.leu.2404548Titel-ID: cdi_proquest_miscellaneous_817602534
- Format
- –
- Schlagworte
- Acute Disease, Acute myeloid leukemia, Aged, AML1 protein, Bacteriophage typing, Binding, Biological and medical sciences, Cell Line, Tumor - metabolism, Chromosome translocations, Chromosomes, Human, Pair 21 - genetics, Chromosomes, Human, Pair 21 - ultrastructure, Chromosomes, Human, Pair 8 - genetics, Chromosomes, Human, Pair 8 - ultrastructure, Core Binding Factor Alpha 2 Subunit - genetics, Core Binding Factor Alpha 2 Subunit - physiology, Drug delivery, Drug Delivery Systems, Drug Screening Assays, Antitumor, Endocytosis, ETO protein, Expression vectors, Female, Fusion protein, Gene expression, Gene Expression Profiling, Gene therapy, Genetic aspects, Genetic Therapy, Health aspects, Hematologic and hematopoietic diseases, Humans, Integrin alpha4beta1 - antagonists & inhibitors, Integrin alpha4beta1 - metabolism, Leukemia, Leukemia, Myeloid - genetics, Leukemia, Myeloid - pathology, Leukemia, Myeloid, Acute - genetics, Leukemia, Myeloid, Acute - pathology, Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis, Libraries, Ligands, Medical sciences, Methods, Neoplasm Proteins - genetics, Neoplasm Proteins - physiology, Neoplastic Stem Cells - metabolism, Oligopeptides - isolation & purification, Oligopeptides - metabolism, Oligopeptides - pharmacology, Oncogene Proteins, Fusion - genetics, Oncogene Proteins, Fusion - physiology, Peptide libraries, Peptide Library, Peptides, Phage display, Phages, Protein Binding, Receptors, Receptors, Drug - antagonists & inhibitors, Receptors, Drug - metabolism, RUNX1 Translocation Partner 1 Protein, Side effects, Therapeutic targets, Translocation, Translocation, Genetic, VLA-4 antigen