Notches, NF-kBs and the Making of T Cell Leukemia

Iannis Aifantis, Tomas Vilimas and Silvia Buonamici

volume 6 | issue 4

15 February 2007
Pages: 403 - 406

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T cell lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer frequent within pediatric ALL patients. Recent findings suggested that the transmembrane receptor NOTCH1 is the major oncogene for the majority of T-ALL cases. In these cases activating mutations of NOTCH1 are responsible for the transformation of developing T cell progenitors. These observations prompted us to study the mechanisms of Notch1-induced T cell transformation. Using parallel studies in T cell progenitors and established T-ALL lines we have demonstrated that the NF-kB signaling pathway is targeted and induced by Notch1 activation. Our studies suggested that the NF-kB activation by Notch1 can be direct, as Notch1 can bind and activate the promoters of the RELB and NFKB2 factors and indirect, as Notch1 can form a complex with the NF-kB kinase IKK. NF-kB appears to be important for the development of the disease as suppression of the pathway antagonizes T cell transformation both in vitro and in vivo, using animal models of T-ALL. We believe that these findings could be important for the understanding of Notch1 signaling and the therapeutic treatment of T-ALL.

Authors

Iannis Aifantis

New York University School of Medicine, New York, NY

Tomas Vilimas

Northwestern University School of Medicine, Chicago, IL

Silvia Buonamici