Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed Study and Hematopathology Analysis of Patient-Derived Specimens

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Katja KarjalainenRenata Pasqualini

Abstract

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. 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. 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 t...Continue Reading

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Citations

Jun 17, 2010·BMC Evolutionary Biology·Carolyn T A HerzigJanice C Telfer
Jan 8, 2011·The Journal of Allergy and Clinical Immunology·Maya ZimmermannCezmi A Akdis
Feb 22, 2011·Molecular Immunology·Emilie Domange JordöMikael C I Karlsson
Jun 21, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Juliane LokauChristoph Garbers
Jun 5, 2019·Growth Factors·Paul M NguyenTracy L Putoczki
Jul 13, 2017·Proceedings of the National Academy of Sciences of the United States of America·Valerae O LewisWadih Arap

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