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 › Academic › peer-review

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
Journal	Cancer Research
Volume	78
Issue number	20
DOIs	https://doi.org/10.1158/0008-5472.CAN-18-0250
Publication status	Published - 2018

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10.1158/0008-5472.CAN-18-0250

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@article{481b153ad1154607ba544616f51f9200,

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.}",

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",

}

VEGFC antibody therapy drives differentiation of AML. / Kampen, Kim R.; Scherpen, Frank J. G.; Mahmud, Hasan; ter Elst, Arja; Mulder, André B.; Guryev, Victor; Verhagen, Han J. M. P.; de Keersmaecker, Kim; Smit, Linda; Kornblau, Steven M.; de Bont, Eveline S. J. M.

In: Cancer Research, Vol. 78, No. 20, 2018, p. 5940-5948.

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

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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30185550

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

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