GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.
Caroline PabstAnne BergeronVincent-Philippe LavalléeJonathan YehPatrick GendronGudmundur L NorddahlJana KroslIsabel BoivinEric DeneaultJessica SimardSuzan ImrenGeneviève BoucherKolja EppertTobias HeroldStefan K BohlanderKeith HumphriesSébastien LemieuxJosée HébertGuy SauvageauFrédéric BarabéPublished in: Blood (2016)
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.
Keyphrases
- acute myeloid leukemia
- stem cells
- poor prognosis
- fatty acid
- induced apoptosis
- genome wide
- endothelial cells
- allogeneic hematopoietic stem cell transplantation
- cell cycle arrest
- copy number
- binding protein
- pluripotent stem cells
- long non coding rna
- induced pluripotent stem cells
- gene expression
- signaling pathway
- mesenchymal stem cells
- single cell
- cystic fibrosis
- endoplasmic reticulum stress
- pseudomonas aeruginosa
- bone marrow
- risk assessment
- climate change
- biofilm formation
- transcription factor
- genome wide identification