Constitutive NF-κB activation in AML: Causes and treatment strategies.
For more than a decade, it has been known that NF-κB is constitutively activated in a majority of acute myeloid leukemia (AML) patients which contributes to the resistance to apoptosis. Inhibition of NF-κB has been shown to induce apoptosis in AML cells, but the clinical effectiveness of NF-κB inhibitors has been inadequate. In recent years, possible causes underlying this continuous NF-κB activity have been elucidated. It has been shown that chromosomal translocations or mutations leading to development of leukemia drive the increase in NF-κB activity. Furthermore, autocrine/paracrine cytokine signaling and increased expression of NF-κB signaling components play an important role in the continuous NF-κB activation. Moreover, high proteasome activity, which positively regulates NF-κB activity, is often observed in AML patients. In the present study, we described these underlying molecular mechanisms leading to constitutive NF-κB activity and discussed the novel treatment strategies based on the inhibition of NF-κB activation.
['Bosman|Matthieu Cornelis Johannes|MC|', 'Schuringa|Jan Jacob|JJ|', 'Vellenga|Edo|E|']
D017209:Apoptosis D006410:Hematopoiesis D006801:Humans D015470:Leukemia, Myeloid, Acute D058990:Molecular Targeted Therapy D009154:Mutation D016328:NF-kappa B D015398:Signal Transduction D014178:Translocation, Genetic
NF-κB AML Apoptosis Survival