GPR56 contributes to the development of acute myeloid leukemia in mice

Item Type:	Article
Title:	GPR56 contributes to the development of acute myeloid leukemia in mice
Creators Name:	Daria, D. and Kirsten, N. and Muranyi, A. and Mulaw, M. and Ihme, S. and Kechter, A. and Hollnagel, M. and Bullinger, L. and Döhner, K. and Döhner, H. and Feuring-Buske, M. and Buske, C.
Abstract:	The G protein-coupled receptor 56 (GPR56) was identified as part of the molecular signature of functionally validated leukemic stem cells isolated from patients with acute myeloid leukemia (AML). This report now demonstrates particularly high expression of GPR56 in patients with mutant NPM1 and FLT3-length mutation and association of high GPR56 expression with inferior prognosis in a large patient cohort treated in two independent multicenter phase III trials. Functional relevance of GPR56 expression was validated in mice, in which co-expression of Gpr56 significantly accelerated HOXA9-induced leukemogenesis and vice versa knockdown of Gpr56 delayed onset of HOXA9/MEIS1-induced AML. Overexpression of Gpr56 grossly changed the molecular phenotype of Hoxa9-transduced cells affecting pathways involved in G protein-coupled receptors (GPRCs) and associated intracellular signaling. Blockage of surface GPR56 by an anti-GPR56 antibody successfully impaired engraftment of primary human AML cells. In summary, these data demonstrate that high expression of GPR56 is able to contribute to AML development and characterize the GPR56 as a potential novel target for antibody-mediated antileukemic strategies.
Keywords:	Acute Myeloid Leukemia, Carcinogenesis, G-Protein-Coupled Receptors, Heterografts, Homeodomain Proteins, Myeloid Ecotropic Viral Integration Site 1 Protein, Neoplasm Proteins, Nucleophosmin, Animals, Mice
Source:	Leukemia
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Volume:	30
Number:	8
Page Range:	1734-1741
Date:	August 2016
Official Publication:	https://doi.org/10.1038/leu.2016.76
PubMed:	View item in PubMed

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