Constitutive NF-κB activation in AML: Causes and treatment strategies

For more than a decade, it has been known that NF-kappa B is constitutively activated in a majority of acute myeloid leukemia (AML) patients which contributes to the resistance to apoptosis. Inhibition of NF-kappa B has been shown to induce apoptosis in AML cells, but the clinical effectiveness of NF-kappa B inhibitors has been inadequate. In recent years, possible causes underlying this continuous NF-kappa B activity have been elucidated. It has been shown that chromosomal translocations or mutations leading to development of leukemia drive the increase in NF-kappa B activity. Furthermore, autocrine/paracrine cytokine signaling and increased expression of NF-kappa B signaling components play an important role in the continuous NF-kappa B activation. Moreover, high proteasome activity, which positively regulates NF-kappa B activity, is often observed in AML patients. In the present study, we described these underlying molecular mechanisms leading to constitutive NF-kappa B activity and discussed the novel treatment strategies based on the inhibition of NF-kappa B activation. (C)2015 Elsevier Ireland Ltd. All rights reserved.