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;
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;
Blood. 2016 Apr 21;127(16):2018-27. doi: 10.1182/blood-2015-11-683649. Epub 2016 Feb 1.
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.
急性髓系白血病（AML）是一种遗传异质性血液恶性肿瘤，由极少数白血病干细胞（LSC）引发和驱动。尽管鉴定常见 LSC 表型存在困难，但越来越多的证据表明，高表达干细胞基因特征与不良临床结果相关。因此，在这种疾病中鉴定功能上不同的亚群对于剖析 LSC 自我更新的分子机制至关重要。在这里，我们结合下一代测序技术和体内 LSC 频率评估，确定了黏附 G 蛋白偶联受体 56（GPR56）作为大多数 AML 样本中人类 LSC 的新型且稳定的标志物。高 GPR56 表达与高危遗传亚组和不良预后显著相关。对 GPR56 表达的分析结合 CD34 表达显示，GPR56(+)细胞在 CD34(-)和 CD34(+)亚群中均具有植入潜力，从而定义了一种独立于 CD34(+)CD38(-)LSC 表型的新型 LSC 区室。
