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Cancer Res. 2017 Dec 1;77(23):6627-6640. doi: 10.1158/0008-5472.CAN-17-1223. Epub 2017 Sep 28.

JAM-C Identifies Src Family Kinase-Activated Leukemia-Initiating Cells and Predicts Poor Prognosis in Acute Myeloid Leukemia.

Author information

1
Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France.
2
Unité de Biostatistique et de Méthodologie, Département de la Recherche Clinique et de l'Innovation, Institut Paoli-Calmettes, Marseille, France.
3
Département de Biopathologie, Cytogénétique et Biologie Moléculaire, Institut Paoli-Calmettes, Marseille, France.
4
Aix Marseille Univ, INSERM, IRD, SESSTIM, Marseille, France.
5
Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France.
6
Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France. michel.aurrand-lions@inserm.fr.

Abstract

Acute myeloid leukemia (AML) originates from hematopoietic stem and progenitor cells that acquire somatic mutations, leading to disease and clonogenic evolution. AML is characterized by accumulation of immature myeloid cells in the bone marrow and phenotypic cellular heterogeneity reflective of normal hematopoietic differentiation. Here, we show that JAM-C expression defines a subset of leukemic cells endowed with leukemia-initiating cell activity (LIC). Stratification of de novo AML patients at diagnosis based on JAM-C-expressing cells frequencies in the blood served as an independent prognostic marker for disease outcome. Using publicly available leukemic stem cell (LSC) gene expression profiles and gene expression data generated from JAM-C-expressing leukemic cells, we defined a single cell core gene expression signature correlated to JAM-C expression that reveals LSC heterogeneity. Finally, we demonstrated that JAM-C controls Src family kinase (SFK) activation in LSC and that LIC with exacerbated SFK activation was uniquely found within the JAM-C-expressing LSC compartment. Cancer Res; 77(23); 6627-40. ©2017 AACR.

PMID:
28972073
DOI:
10.1158/0008-5472.CAN-17-1223
[Indexed for MEDLINE]
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