Submitted January 13, 2003
Accepted May 29, 2003
NF-
B activation in premalignant mouse tal-1/scl thymocytes and tumors
Jennifer O'Neil, Juan-Jose Ventura, Nicole Cusson, and Michelle A Kelliher*
Department of Cancer Biology and the Interdisciplinary Graduate Program, University of Massachusetts Medical School, Worcester, MA, USA
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
* Corresponding author; email: Michelle.Kelliher{at}umassmed.edu.
TAL-1/SCL activation is a common genetic event in pediatric T cell acute lymphoblastic leukemia (T-ALL). Expression of tal-1/scl or a DNA binding mutant of tal-1/scl induces arrest of thymocyte development, resulting in decreases in double positive and single positive, CD4 thymocytes. Moreover, nuclear p65/p50 heterodimers are detected in premalignant tal-1/scl and mut tal-1/scl thymocytes, suggesting that E2A depletion may induce developmental arrest and stimulate NF-
B activation. Increased NF-B activity is also observed in tal-1/scl tumors and bcl-2 is overexpressed. To examine the contribution of NF-B to tal-1/scl tumor growth in vivo, we expressed a mutant form of IB
in tal-1/scl tumor cells. Although expression of mutant IB inhibited the TNF--induced NF-B response, it had no effect on tumor growth in mice. These data suggest that NF-B activation is an early event in tal-1/scl-induced leukemogenesis, associated with arrest of thymocyte development, and does not appear to contribute to tal-1/scl induced tumor growth.
