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Blood. 2016 Apr 21;127(16):2018-27. doi: 10.1182/blood-2015-11-683649. Epub 2016 Feb 1.

GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.

Author information

1
Laboratory of Molecular Genetics of Stem Cells, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada; Department of Internal Medicine IV, Hematology and Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;
2
Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec, Centre de Recherche en Infectiologie du Centre Hospitalier de l'Université de Laval, Quebec City, QC, Canada;
3
Laboratory of Molecular Genetics of Stem Cells, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada; Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada;
4
Laboratory of Molecular Genetics of Stem Cells, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada;
5
Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada;
6
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada;
7
Department of Pediatrics, Research Institute of the McGill University Health Centre, Montreal Children's Hospital, McGill University, Montreal, QC, Canada.
8
Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany;
9
Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand;
10
Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada; Department of Computer Science and Operations Research, University of Montreal, Montreal, QC, Canada;
11
Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada; Leukemia Cell Bank of Quebec, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada; Department of Medicine, University of Montreal, Montreal, QC, Canada;
12
Laboratory of Molecular Genetics of Stem Cells, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada; Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada; Leukemia Cell Bank of Quebec, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada; Department of Medicine, University of Montreal, Montreal, QC, Canada;
13
Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec, Centre de Recherche en Infectiologie du Centre Hospitalier de l'Université de Laval, Quebec City, QC, Canada; CHU de Québec Hôpital Enfant-Jésus, Quebec City, QC, Canada; and Department of Medicine, University Laval, Quebec City, QC, Canada.

Abstract

Acute myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy, which is initiated and driven by a rare fraction of leukemia stem cells (LSCs). Despite the difficulties of identifying a common LSC phenotype, there is increasing evidence that high expression of stem cell gene signatures is associated with poor clinical outcome. Identification of functionally distinct subpopulations in this disease is therefore crucial to dissecting the molecular machinery underlying LSC self-renewal. Here, we combined next-generation sequencing technology with in vivo assessment of LSC frequencies and identified the adhesion G protein-coupled receptor 56 (GPR56) as a novel and stable marker for human LSCs for the majority of AML samples. High GPR56 expression was significantly associated with high-risk genetic subgroups and poor outcome. Analysis of GPR56 in combination with CD34 expression revealed engraftment potential of GPR56(+)cells in both the CD34(-)and CD34(+)fractions, thus defining a novel LSC compartment independent of the CD34(+)CD38(-)LSC phenotype.

PMID:
26834243
DOI:
10.1182/blood-2015-11-683649
[Indexed for MEDLINE]
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