VEGFC Antibody Therapy Drives Differentiation of AML.
basic_science · Level V
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- Record sourced from PubMed, PMID 30185550.
- Also identified by DOI 10.1158/0008-5472.CAN-18-0250.
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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<sup>+</sup> AML blasts. Treatment of CD34<sup>+</sup> 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<sup>+</sup> AML cell fate decisions via FOXO3A and serve as a new potential differentiation therapy for patients with AML.<b>Significance:</b> These findings reveal VEGFC targeting as a promising new differentiation therapy in AML. <i>Cancer Res; 78(20); 5940-8. ©2018 AACR</i>.
Medical subject headings
- Antibodies, Monoclonal
- Leukemia, Myeloid, Acute
- Vascular Endothelial Growth Factor C