VEGFC Antibody Therapy Drives Differentiation of AML

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

OnderzoeksoutputAcademicpeer review

11 Citaten (Scopus)
133 Downloads (Pure)

Samenvatting

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.

Significance: These findings reveal VEGFC targeting as a promising new differentiation therapy in AML. (C) 2018 AACR.

Originele taal-2English
Pagina's (van-tot)5940-5948
Aantal pagina's9
TijdschriftCancer Research
Volume78
Nummer van het tijdschrift20
Vroegere onlinedatum5-sep.-2018
DOI's
StatusPublished - 15-okt.-2018

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