VEGFC antibody therapy drives differentiation of AML

High expression of vascular endothelial growth factor C (VEGFC) predicts adverse prognosis in acute myeloid leukemia (AML). We therefore explored VEGFC targeting efficacy as an AML therapy using a VEGFC monoclonal antibody. VEGFC antibody therapy enforced myelocytic differentiation of clonal CD34+ AML blasts. Treatment of CD34+ AML blasts with the antibody reduced expansion potential by 30-50% 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 AML patients.

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