Targeting IL11 receptor in leukemia and lymphoma: A functional ligand-directed study and hematopathology analysis of patient-derived specimens

Katja Karjalainen, Diana E. Jaalouk, Carlos Bueso-Ramos, Laura Bover, Yan Sun, Akihiko Kuniyasu, Wouter H.P. Driessen, Marina Cardó-Vila, Cecilia Rietz, Amado J. Zurita, Susan O'Brien, Hagop M. Kantarjian, Jorge E. Cortes, George A. Calin, Erkki Koivunen, Wadih Arap, Renata Pasqualini

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Purpose: The IL11 receptor (IL11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors, such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here, we evaluated the IL11R as a candidate therapeutic target in human leukemia and lymphoma. Experimental Design and Results: First, we show that the IL11R protein is expressed in a variety of human leukemia-and lymphoma-derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, whereas expression is absent from nonmalignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11), specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analogue with an apparent improved antileukemia cell profile. Conclusions: These results indicate (i) that the IL11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases.

Original languageEnglish (US)
Pages (from-to)3041-3051
Number of pages11
JournalClinical Cancer Research
Volume21
Issue number13
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Targeting IL11 receptor in leukemia and lymphoma: A functional ligand-directed study and hematopathology analysis of patient-derived specimens'. Together they form a unique fingerprint.

  • Cite this

    Karjalainen, K., Jaalouk, D. E., Bueso-Ramos, C., Bover, L., Sun, Y., Kuniyasu, A., Driessen, W. H. P., Cardó-Vila, M., Rietz, C., Zurita, A. J., O'Brien, S., Kantarjian, H. M., Cortes, J. E., Calin, G. A., Koivunen, E., Arap, W., & Pasqualini, R. (2015). Targeting IL11 receptor in leukemia and lymphoma: A functional ligand-directed study and hematopathology analysis of patient-derived specimens. Clinical Cancer Research, 21(13), 3041-3051. https://doi.org/10.1158/1078-0432.CCR-13-3059