Format

Send to

Choose Destination
Clin Cancer Res. 2015 Jul 1;21(13):3041-51. doi: 10.1158/1078-0432.CCR-13-3059. Epub 2015 Mar 16.

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

Author information

1
Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Department of Biological and Environmental Science, The University of Helsinki, Helsinki, Finland.
2
Department of Biology, American University of Beirut, Beirut, Lebanon.
3
Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
4
Department of Genomic Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
5
Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
6
Department of Molecular Cell Pharmacology, Sojo University, Kumamoto, Japan.
7
Roche, Basel, Switzerland.
8
University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico. Division of Molecular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico.
9
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
10
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
11
Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
12
Department of Biological and Environmental Science, The University of Helsinki, Helsinki, Finland. Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
13
University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico. Division of Hematology/Oncology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico. rpasqual@salud.unm.edu warap@salud.unm.edu.
14
University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico. Division of Molecular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico. rpasqual@salud.unm.edu warap@salud.unm.edu.

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.

PMID:
25779950
PMCID:
PMC4490100
DOI:
10.1158/1078-0432.CCR-13-3059
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center