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Blood Adv. 2017 Aug 28;1(20):1635-1644. doi: 10.1182/bloodadvances.2017005694. eCollection 2017 Sep 12.

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

Author information

1
Division of Hematology, Department of Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
2
Vasgene Therapeutics, Inc, Los Angeles, CA.
3
Division of Hematology and Medical Oncology and.
4
Knight Cancer Institute, Oregon Health and Science University, Portland, OR.
5
Howard Hughes Medical Institute, Chevy Chase, MD; and.
6
Department of Cell, Developmental, and Cancer Biology, Oregon Health and Science University, Portland, OR.

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.

Conflict of interest statement

Conflict-of-interest disclosure: A.A.M. received research funding and served as a consultant for Pfizer, Inc. J.W.T. received research support from Aptose, Array, AstraZeneca, Constellation, Genentech, Gilead, Incyte, Janssen, Seattle Genetics, Syros, and Takeda and is on the Scientific Advisory Board for Leap Oncology. The remaining authors declare no competing financial interests.

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