1: Blood. 2003 Oct 1;102(7):2593-6. Epub 2003 Jun 19. 

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

O'Neil J, Ventura JJ, Cusson N, Kelliher M.

Department of Cancer Biology, University of Massachusetts Medical School,
Worcester, USA.

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

PMID: 12816868 [PubMed - indexed for MEDLINE]


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