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

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.

SUBMITTER: Merchant AA

PROVIDER: S-EPMC5728330 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Merchant Akil A AA Jorapur Aparna A McManus Amy A Liu Ren R Krasnoperov Valery V Chaudhry Parvesh P Singh Mohan M Harton Lisa L Agajanian Mary M Kim Miriam M Triche Timothy J TJ Druker Brian J BJ Tyner Jeffrey W JW Gill Parkash S PS

Blood advances 20170828 20

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/AK ...[more]

PMID: 29296810

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