Targeting the NF-|[kappa]|B signaling pathway in Notch1-induced T-cell leukemia

摘要: T-cell acute lymphoblastic leukemia (T-ALL), unlike other ALL types, is only infrequently associated with chromosomal aberrations, but it was recently shown that most individuals T-ALL carry activating mutations in the NOTCH1 gene. However, signaling pathways and target genes responsible for Notch1-induced neoplastic transformation remain undefined. We report here constitutively active Notch1 activates NF-kappaB pathway transcriptionally via IkappaB kinase (IKK) complex, thereby causing increased expression of several well characterized bone marrow hematopoietic stem cells progenitors. Our observations demonstrate highly established human inhibition can efficiently restrict tumor growth both vitro vivo. These findings identify as one major mediators suggest a potential future therapies T-ALL.