title: Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed Study and Hematopathology Analysis of Patient-Derived Specimens.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Katja
authors.initials: K
authors.lastname: Karjalainen
authors.affiliation: Department of Biology, American University of Beirut, Beirut, Lebanon.
authors.forename: Diana E
authors.initials: DE
authors.lastname: Jaalouk
authors.affiliation: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.affiliation: Department of Genomic Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Laura
authors.initials: L
authors.lastname: Bover
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Molecular Cell Pharmacology, Sojo University, Kumamoto, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kuniyasu
authors.affiliation: Roche, Basel, Switzerland.
authors.forename: Wouter H P
authors.initials: WH
authors.lastname: Driessen
authors.affiliation: 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.
authors.forename: Marina
authors.initials: M
authors.lastname: Cardó-Vila
authors.affiliation: 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.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rietz
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Amado J
authors.initials: AJ
authors.lastname: Zurita
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.affiliation: 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.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: 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.
authors.forename: Erkki
authors.initials: E
authors.lastname: Koivunen
authors.affiliation: 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.
authors.forename: Wadih
authors.initials: W
authors.lastname: Arap
authors.affiliation: 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.
authors.forename: Renata
authors.initials: R
authors.lastname: Pasqualini
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy*; D008024:Ligands; D008223:Lymphoma / Q000188:drug therapy*; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D053702:Receptors, Interleukin-11 / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D010455:Peptides; D053702:Receptors, Interleukin-11; C000601739:bone metastasis-targeting peptidomimetic-11