journal contribution
posted on 2023-03-31, 02:07 authored by 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 Complete supplementary Data file including supportive figures that highlight: VEGFC targeting potential in pediatric AML, VEGFC/KDR complex molecular targeting in AML, and VEGFC antibody induced differentiation phenotype in AML, and supplementary tables include the patient characteristics, used antibodies and primer sequences, and FLT3-ITD ratio's
Funding
Pediatric Oncology Groningen
Foundation Beatrix Children
Jan Kornelis de Cock Stichting
AML
History
ARTICLE 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.Significance: These findings reveal VEGFC targeting as a promising new differentiation therapy in AML. Cancer Res; 78(20); 5940–8. ©2018 AACR.
