NF-κB activation in premalignant mouse tal-1/scl thymocytes and tumors

Abstract

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-κB activation. Increased NF-κB activity is also observed in tal-1/scl tumors and bcl-2 is overexpressed. To examine the contribution of NF-κB to tal-1/scl tumor growth in vivo, we expressed a mutant form of IκBα in tal-1/scl tumor cells. Although expression of mutant IκBα inhibited the tumor necrosis factor alpha (TNF-α)-induced NF-κB response, it had no effect on tumor growth in mice. These data suggest that NF-κB 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. (Blood. 2003;102:2593-2596)