Over-expression of Flt3 induces NF-κB pathway and increases the expression of IL-6

Activating mutations or over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and other signaling pathways. In this study, we addressed the role of Flt3 in the activation of nuclear factor-kappa B (NF-kappa B); which is a target molecule of these kinase pathways. In BaF3 cells stably expressing 1710, a NF-kappa B-responsive reporter was upregulated and its target gene, IL-6, was increased by the involvement of Flt3-ERK/MAPK-NF-kappa B pathway. Furthermore, we found a modest positive correlation (r = 0.35, p = 0.096) between Flt3 and IL-6 mRNA expression in 24 AML specimens. These results suggest a role of Flt3 overexpression in NF-kappa B pathway. (c) 2005 Elsevier Ltd. All rights reserved.