Targeting neuropilin-1 in human leukemia and lymphoma

Katja Karjalainen, Diana E. Jaalouk, Carlos E. Bueso-Ramos, Amado J. Zurita, Akihiko Kuniyasu, Bedrich L. Eckhardt, Frank C. Marini, Benjamin Lichtiger, Susan O'Brien, Hagop M. Kantarjian, Jorge E. Cortes, Erkki Koivunen, Wadih Arap, Renata Pasqualini

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Targeted drug delivery offers an opportunity for the development of safer and more effective therapies for the treatment of cancer. In this study, we sought to identify short, cell-internalizing peptide ligands that could serve as directive agents for specific drug delivery in hematologic malignancies. By screening of human leukemia cells with a combinatorial phage display peptide library, we isolated a peptide motif, sequence Phe-Phe/Tyr-Any-Leu-Arg-Ser (FF/YXLRS), which bound to different leukemia cell lines and to patient-derived bone marrow samples. The motif was internalized through a receptor-mediated pathway, and we next identified the corresponding receptor as the transmembrane glycoprotein neuropilin-1 (NRP-1). Moreover, we observed a potent anti-leukemia cell effect when the targeting motif was synthesized in tandem to the pro-apoptotic sequence D(KLAKLAK)2. Finally, our results confirmed increased expression of NRP-1 in representative human leukemia and lymphoma cell lines and in a panel of bone marrow specimens obtained from patients with acute lymphoblastic leukemia or acute myelogenous leukemia compared with normal bone marrow. These results indicate that NRP-1 could potentially be used as a target for liganddirected therapy in human leukemias and lymphomas and that the prototype CGFYWLRSC-GG- D(KLAKLAK)2 is a promising drug candidate in this setting.

Original languageEnglish (US)
Pages (from-to)920-927
Number of pages8
JournalBlood
Volume117
Issue number3
DOIs
StatePublished - Jan 20 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Karjalainen, K., Jaalouk, D. E., Bueso-Ramos, C. E., Zurita, A. J., Kuniyasu, A., Eckhardt, B. L., Marini, F. C., Lichtiger, B., O'Brien, S., Kantarjian, H. M., Cortes, J. E., Koivunen, E., Arap, W., & Pasqualini, R. (2011). Targeting neuropilin-1 in human leukemia and lymphoma. Blood, 117(3), 920-927. https://doi.org/10.1182/blood-2010-05-282921