VEGFC Antibody Therapy Drives Differentiation of AML.

Autor:	Kampen KR; Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. kim.kampen@kuleuven.be edebont@elkerliek.nl.; Laboratory for Disease Mechanisms in Cancer, Department of Oncology, KU Leuven, University of Leuven, Leuven Cancer Institute (LKI), Leuven, Belgium., Scherpen FJG; Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Mahmud H; Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Ter Elst A; Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Mulder AB; Department of Laboratory Medicine, University Medical Center Groningen, Groningen, the Netherlands., Guryev V; European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Verhagen HJMP; Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands., De Keersmaecker K; Laboratory for Disease Mechanisms in Cancer, Department of Oncology, KU Leuven, University of Leuven, Leuven Cancer Institute (LKI), Leuven, Belgium., Smit L; Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands., Kornblau SM; Department of Leukemia, The University of Texas M.D. Anderson Cancer, Houston, Texas., De Bont ESJM; Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. kim.kampen@kuleuven.be edebont@elkerliek.nl.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2018 Oct 15; Vol. 78 (20), pp. 5940-5948. Date of Electronic Publication: 2018 Sep 05.
DOI:	10.1158/0008-5472.CAN-18-0250
Abstrakt:	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 . (©2018 American Association for Cancer Research.)
Databáze:	MEDLINE
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