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 Blood, 1 July 2006, Vol. 108, No. 1, pp. 305-310.
Prepublished online as a Blood First Edition Paper on February 28, 2006; DOI 10.1182/blood-2006-01-0143.

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NEOPLASIA

Notch1-dependent lymphomagenesis is assisted by but does not essentially require pre-TCR signaling

Antonio F. Campese, Annette I. Garbe, Fangrong Zhang, Fabio Grassi, Isabella Screpanti, and Harald von Boehmer

From Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA; the Department of Experimental Medicine and Pathology, University "La Sapienza," Rome, Italy; and the Institute for Research in Biomedicine, Bellinzona, Switzerland.

Overexpression of intracellular Notch plays an important role in the generation of human acute lymphoblastic T cell leukemia (T-ALL). In mouse models, it was shown that Notch-dependent T-ALL required pre-TCR signaling. Here we show that pre-TCR signaling is required to condition mice for Notch-dependent transformation but that it is not required to sustain malignant growth of T-ALL. In contrast to previous studies, we found that disease development does not require pre-TCR but that it can be accelerated in Rag2-/- mice by transient mimicking of pre-TCR signals. (Blood. 2006;108:305-310)


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