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

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Armstrong, Florence | de la Grange, Philippe Brunet | Gerby, Bastien | Rouyez, Marie-Christine | Calvo, Julien | Fontenay, Michaéla | Boissel, Nicolas | Dombret, Hervé | Baruchel, André | Landman-Parker, Judith | Roméo, Paul-Henri | Ballerini, Paola | Pflumio, Françoise

Edité par CCSD ; American Society of Hematology -

International audience. Abstract 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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