Department of Cancer Biology; Department of Molecular Genetics and Microbiology
Animals; Antigens, CD4; Antigens, CD8; Basic Helix-Loop-Helix Transcription Factors; DNA-Binding Proteins; Gene Expression Regulation, Leukemic; I-kappa B Proteins; Mice; Mice, Mutant Strains; NF-kappa B; NF-kappa B p50 Subunit; Precancerous Conditions; Precursor Cell Lymphoblastic; Leukemia-Lymphoma; Proto-Oncogene Proteins; T-Lymphocytes; Thymus Gland; Thymus Neoplasms; Transcription Factor RelA; Transcription Factors
Cancer Biology | Microbiology | Molecular Genetics
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.
DOI of Published Version
Blood. 2003 Oct 1;102(7):2593-6. Epub 2003 Jun 19. Link to article on publisher's site
O'Neil, Jennifer Elinor; Ventura, Juan-Jose; Hermance, Nicole M.; and Kelliher, Michelle A., "NF-kappaB activation in premalignant mouse tal-1/scl thymocytes and tumors" (2003). Open Access Articles. 279.