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GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.
Pabst C, Bergeron A, Lavallée VP, Yeh J, Gendron P, Norddahl GL, Krosl J, Boivin I, Deneault E, Simard J, Imren S, Boucher G, Eppert K, Herold T, Bohlander SK, Humphries K, Lemieux S, Hébert J, Sauvageau G, Barabé F. Blood, 2016 [Epub ahead of print]
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 to identify 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 dissect the molecular machinery underlying LSC self-renewal. Here, we combined Next-Generation-Sequencing (NGS) 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.