Reports summarize acute myeloid leukemia therapy research from Johann Wolfgang Goethe University

03-16-2007

A new study, "Interleukin-18 directly activates T-bet expression and function via p38 mitogen-activated protein kinase and nuclear factor-kappaB in acute myeloid leukemia-derived predendritic KG-1 cells," is now available. According to recent research from Frankfurt am Main, Germany, "The leukemic cell line KG-1 was isolated from a patient with acute myeloid leukemia and is regarded a cellular model of human dendritic cell progenitors. The T helper type 1 cytokine interleukin (IL)-18 has been shown to induce the maturation of these cells towards a dendritic phenotype and, moreover, is able to mediate IFNgamma production in this model."

"Because T-box expressed in T cells (T-bet) is considered to be of paramount importance for dendritic cell function, the effects of IL-18 on this transcription factor have been investigated in the current study. Here, we show that activation of KG-1 cells by IL-18 induces T-bet mRNA and protein within 4 to 6 h of incubation. This hitherto unrecognized function of IL-18 was suppressed by the inhibition of p38 mitogen-activated protein kinase activity and nuclear factor-kappaB function. Blockage of translation by cycloheximide, usage of neutralizing antibodies, and the inability of IFNgamma to mediate significant p38 mitogen-activated protein kinase activation in KG-1 cells clearly revealed that activation of T-bet was not via autocrine IFNgamma. T-bet function was evaluated by short interfering RNA technology. Notably, specific suppression of T-bet induction impaired secretion of IFNgamma by KG-1 cells under the influence of IL-18. Therapeutic application of IL-18 has the potential to profoundly affect the biology of acute myeloid leukemia predendritic cells such as KG-1 cells," wrote M. Bachmann and colleagues, Johann Wolfgang Goethe University.

The researchers concluded: "Under these conditions, activation of T-bet may play a key role in processes that have the potential to correct the T helper type 1 deficiency associated with leukemia-mediated immunosuppression."

Bachmann and colleagues published their study in Molecular Cancer Therapeutics (Interleukin-18 directly activates T-bet expression and function via p38 mitogen-activated protein kinase and nuclear factor-kappaB in acute myeloid leukemia-derived predendritic KG-1 cells. Molecular Cancer Therapeutics, 2007;6(2):723-31).

For additional information, contact M. Bachmann, Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universitat, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.

Publisher contact information for the journal Molecular Cancer Therapeutics is: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.