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Animal Models

GPR56 contributes to the development of acute myeloid leukemia in mice

Leukemia volume 30, pages 1734–1741 (2016)Cite this article

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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.

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Acknowledgements

We thank the Core Facility FACS, Ulm University and the team of the animal facility at Ulm University. The work was supported by Research Training Group CEMMA funded by the DFG (to NK) and the Z1 project of the SFB 1074 funded by the DFG (to CB).

Author contributions

DD, NK, AM, MM, SI, MH, LB, KD and HD provided patient samples and analyzed data. MF and CB designed the research, analyzed the data and wrote the manuscript.

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  1. D Daria and N Kirsten: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute for Experimental Cancer Research, Comprehensive Cancer Center, University Hospital of Ulm, Ulm, Germany

    D Daria, N Kirsten, A Muranyi, M Mulaw, S Ihme, A Kechter, M Hollnagel & C Buske

  2. Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany

    L Bullinger, K Döhner, H Döhner & M Feuring-Buske

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  1. D Daria
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Correspondence to C Buske.

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Daria, D., Kirsten, N., Muranyi, A. et al. GPR56 contributes to the development of acute myeloid leukemia in mice. Leukemia 30, 1734–1741 (2016). https://doi.org/10.1038/leu.2016.76

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