VEGFC antibody therapy drives differentiation of AML

Kim R. Kampen; Frank J.G. Scherpen; Hasan Mahmud; Arja Ter Elst; André B. Mulder; Victor Guryev; Han J.M.P. Verhagen; Kim De Keersmaecker; Linda Smit; Steven M. Kornblau; Eveline S.J.M. De Bont

doi:10.1158/0008-5472.CAN-18-0250

VEGFC antibody therapy drives differentiation of AML

Kim R. Kampen
, Frank J.G. Scherpen
, Hasan Mahmud
, Arja Ter Elst
, André B. Mulder
, Victor Guryev
, Han J.M.P. Verhagen
, Kim De Keersmaecker
, Linda Smit
, Steven M. Kornblau
, Eveline S.J.M. De Bont

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

High expression of VEGFC predicts adverse prognosis in acute myeloid leukemia (AML). We therefore explored VEGFC-targeting efficacy as an AML therapy using a VEGFC mAb. VEGFC antibody therapy enforced myelocytic differentiation of clonal CD34⁺ AML blasts. Treatment of CD34⁺ AML blasts with the antibody reduced expansion potential by 30% to 50% and enhanced differentiation via FOXO3A suppression and inhibition of MAPK/ERK proliferative signals. VEGFC antibody therapy also accelerated leukemia cell differentiation in a systemic humanized AML mouse model. Collectively, these results define a regulatory function of VEGFC in CD34⁺ AML cell fate decisions via FOXO3A and serve as a new potential differentiation therapy for patients with AML.

Original language	English
Pages (from-to)	5940-5948
Number of pages	9
Journal	Cancer Research
Volume	78
Issue number	20
DOIs	https://doi.org/10.1158/0008-5472.CAN-18-0250
State	Published - 2018
Externally published	Yes

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@article{0df1907c282e4d5e9e4fc5758e8f9dfc,

title = "VEGFC antibody therapy drives differentiation of AML",

abstract = "High expression of VEGFC predicts adverse prognosis in acute myeloid leukemia (AML). We therefore explored VEGFC-targeting efficacy as an AML therapy using a VEGFC mAb. VEGFC antibody therapy enforced myelocytic differentiation of clonal CD34+ AML blasts. Treatment of CD34+ AML blasts with the antibody reduced expansion potential by 30\% to 50\% and enhanced differentiation via FOXO3A suppression and inhibition of MAPK/ERK proliferative signals. VEGFC antibody therapy also accelerated leukemia cell differentiation in a systemic humanized AML mouse model. Collectively, these results define a regulatory function of VEGFC in CD34+ AML cell fate decisions via FOXO3A and serve as a new potential differentiation therapy for patients with AML.",

author = "Kampen, \{Kim R.\} and Scherpen, \{Frank J.G.\} and Hasan Mahmud and \{Ter Elst\}, Arja and Mulder, \{Andr{\'e} B.\} and Victor Guryev and Verhagen, \{Han J.M.P.\} and \{De Keersmaecker\}, Kim and Linda Smit and Kornblau, \{Steven M.\} and \{De Bont\}, \{Eveline S.J.M.\}",

note = "Publisher Copyright: {\textcopyright} 2018 American Association for Cancer Research.",

year = "2018",

doi = "10.1158/0008-5472.CAN-18-0250",

language = "English",

volume = "78",

pages = "5940--5948",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

number = "20",

}

TY - JOUR

T1 - VEGFC antibody therapy drives differentiation of AML

AU - Kampen, Kim R.

AU - Scherpen, Frank J.G.

AU - Mahmud, Hasan

AU - Ter Elst, Arja

AU - Mulder, André B.

AU - Guryev, Victor

AU - Verhagen, Han J.M.P.

AU - De Keersmaecker, Kim

AU - Smit, Linda

AU - Kornblau, Steven M.

AU - De Bont, Eveline S.J.M.

PY - 2018

Y1 - 2018

N2 - High expression of VEGFC predicts adverse prognosis in acute myeloid leukemia (AML). We therefore explored VEGFC-targeting efficacy as an AML therapy using a VEGFC mAb. VEGFC antibody therapy enforced myelocytic differentiation of clonal CD34+ AML blasts. Treatment of CD34+ AML blasts with the antibody reduced expansion potential by 30% to 50% and enhanced differentiation via FOXO3A suppression and inhibition of MAPK/ERK proliferative signals. VEGFC antibody therapy also accelerated leukemia cell differentiation in a systemic humanized AML mouse model. Collectively, these results define a regulatory function of VEGFC in CD34+ AML cell fate decisions via FOXO3A and serve as a new potential differentiation therapy for patients with AML.

AB - High expression of VEGFC predicts adverse prognosis in acute myeloid leukemia (AML). We therefore explored VEGFC-targeting efficacy as an AML therapy using a VEGFC mAb. VEGFC antibody therapy enforced myelocytic differentiation of clonal CD34+ AML blasts. Treatment of CD34+ AML blasts with the antibody reduced expansion potential by 30% to 50% and enhanced differentiation via FOXO3A suppression and inhibition of MAPK/ERK proliferative signals. VEGFC antibody therapy also accelerated leukemia cell differentiation in a systemic humanized AML mouse model. Collectively, these results define a regulatory function of VEGFC in CD34+ AML cell fate decisions via FOXO3A and serve as a new potential differentiation therapy for patients with AML.

UR - https://www.scopus.com/pages/publications/85054892789

U2 - 10.1158/0008-5472.CAN-18-0250

DO - 10.1158/0008-5472.CAN-18-0250

M3 - Article

C2 - 30185550

AN - SCOPUS:85054892789

SN - 0008-5472

VL - 78

SP - 5940

EP - 5948

JO - Cancer Research

JF - Cancer Research

IS - 20

ER -

VEGFC antibody therapy drives differentiation of AML

Abstract

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