EPHB4 is a therapeutic target in AML and promotes leukemia cell survival via AKT

Akil A. Merchant; Aparna Jorapur; Amy McManus; Ren Liu; Valery Krasnoperov; Parvesh Chaudhry; Mohan Singh; Lisa Harton; Mary Agajanian; Miriam Kim; Timothy J. Triche, Jr; Brian J. Druker; Jeffrey W. Tyner; Parkash S. Gill

Blood Advances (Sep 2017)

EPHB4 is a therapeutic target in AML and promotes leukemia cell survival via AKT

Akil A. Merchant,
Aparna Jorapur,
Amy McManus,
Ren Liu,
Valery Krasnoperov,
Parvesh Chaudhry,
Mohan Singh,
Lisa Harton,
Mary Agajanian,
Miriam Kim,
Timothy J. Triche, Jr,
Brian J. Druker,
Jeffrey W. Tyner,
Parkash S. Gill

Affiliations

Akil A. Merchant: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;; Akil A. Merchant, Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1450 Biggy St, Norris Research Tower 3501, Los Angeles, CA 90033;
Aparna Jorapur: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;
Amy McManus: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;
Ren Liu: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;
Valery Krasnoperov: Vasgene Therapeutics, Inc, Los Angeles, CA;
Parvesh Chaudhry: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;
Mohan Singh: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;
Lisa Harton: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;
Mary Agajanian: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;
Miriam Kim: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;
Timothy J. Triche, Jr: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;
Brian J. Druker: Division of Hematology and Medical Oncology and; Knight Cancer Institute, Oregon Health and Science University, Portland, OR;; Howard Hughes Medical Institute, Chevy Chase, MD; and
Jeffrey W. Tyner: Knight Cancer Institute, Oregon Health and Science University, Portland, OR;; Department of Cell, Developmental, and Cancer Biology, Oregon Health and Science University, Portland, OR
Parkash S. Gill: Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;

Journal volume & issue: Vol. 1, no. 20
pp. 1635 – 1644

Abstract

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Abstract: EPHB4, an ephrin type B receptor, is implicated in the growth of several epithelial tumors and is a promising target in cancer therapy; however, little is known about its role in hematologic malignancies. In this article, we show that EPHB4 is highly expressed in ∼30% of acute myeloid leukemia (AML) samples. In an unbiased RNA interference screen of primary leukemia samples, we found that EPHB4 drives survival in a subset of AML cases. Knockdown of EPHB4 inhibits phosphatidylinositol 3-kinase/AKT signaling, and this is accompanied by a reduction in cell viability, which can be rescued by a constitutively active form of AKT. Finally, targeting EPHB4 with a highly specific monoclonal antibody (MAb131) is effective against AML in vitro and in vivo. EPHB4 is therefore a potential target in AML with high EPHB4 expression.

Published in Blood Advances

ISSN: 2473-9529 (Print); 2473-9537 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine
Website: https://ashpublications.org/bloodadvances

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