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

doi:10.1182/bloodadvances.2017005694

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 journal › Article › peer-review

21 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 language	English
Pages (from-to)	1635-1644
Number of pages	10
Journal	Blood Advances
Volume	1
Issue number	20
DOIs	https://doi.org/10.1182/bloodadvances.2017005694
State	Published - Sep 12 2017

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title = "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.",

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

note = "Publisher Copyright: {\textcopyright} 2017 by The American Society of Hematology.",

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doi = "10.1182/bloodadvances.2017005694",

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T1 - EPHB4 is a therapeutic target in AML and promotes leukemia cell survival via AKT

AU - Merchant, Akil A.

AU - Jorapur, Aparna

AU - McManus, Amy

AU - Liu, Ren

AU - Krasnoperov, Valery

AU - Chaudhry, Parvesh

AU - Singh, Mohan

AU - Harton, Lisa

AU - Agajanian, Mary

AU - Kim, Miriam

AU - Triche, Timothy J.

AU - Druker, Brian J.

AU - Tyner, Jeffrey W.

AU - Gill, Parkash S.

PY - 2017/9/12

Y1 - 2017/9/12

N2 - 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.

AB - 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.

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SN - 2473-9529

VL - 1

SP - 1635

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JO - Blood Advances

JF - Blood Advances

IS - 20

ER -

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

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