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Blood. 2009 Feb 19;113(8):1730-40. doi: 10.1182/blood-2008-02-138172. Epub 2008 Nov 4.

NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity.

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  • 1Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 8104 Paris, France.


Understanding the pathways that regulate the human T-cell acute lymphoblastic leukemia (T-ALL) initiating cells (T-LiC) activity has been hampered by the lack of biologic assays in which this human disease can be studied. Here we show that coculture of primary human T-ALL with a mouse stromal cell line expressing the NOTCH ligand delta-like-1 (DL1) reproducibly allowed maintenance of T-LiC and long-term growth of blast cells. Human T-ALL mutated or not on the NOTCH receptor required sustained activation of the NOTCH pathway via receptor/ligand interaction for growth and T-LiC activity. On the reverse, inhibition of the NOTCH pathway during primary cultures abolished in vitro cell growth and in vivo T-LiC activity. Altogether, these results demonstrate the major role of the NOTCH pathway activation in human T-ALL development and in the maintenance of leukemia-initiating cells.

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