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, Brian J. Druker, Jeffrey W. Tyner, Parkash S. Gill

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1635-1644
Number of pages10
JournalBlood Advances
Volume1
Issue number20
DOIs
StatePublished - Sep 12 2017

ASJC Scopus subject areas

  • Hematology

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    Merchant, A. A., Jorapur, A., McManus, A., Liu, R., Krasnoperov, V., Chaudhry, P., Singh, M., Harton, L., Agajanian, M., Kim, M., Triche, T. J., Druker, B. J., Tyner, J. W., & Gill, P. S. (2017). EPHB4 is a therapeutic target in AML and promotes leukemia cell survival via AKT. Blood Advances, 1(20), 1635-1644. https://doi.org/10.1182/bloodadvances.2017005694