Nuclear factor‐KappaB modulation as a therapeutic approach in hematologic malignancies

Publisher Website
Google Scholar
Abstract
Nuclear factor‐kappaB (NF‐κB) is a collective term that refers to a small class of dimeric transcription factors for a number of genes, including growth factors, angiogenesis modulators, cell‐adhesion molecules, and antiapoptotic factors. Although most NF‐κB proteins promote transcription, some act as inactivating or repressive complexes. The most common p50‐RelA (p65) dimer known “specifically” as NF‐κB, is relatively abundant, controls the expression of numerous genes, and exists as an inactive cytoplasmic complex bound to inhibitory proteins of the NF‐κB inhibitor (IκB) family. The inactive NF‐κB‐IκB complex is activated by a variety of stimuli, including proinflammatory cytokines, mitogens, growth factors, and stress‐inducing agents. The release of NF‐κB facilitates its translocation to the nucleus, where it promotes cell survival by initiating the transcription of genes encoding stress‐response enzymes, cell‐adhesion molecules, proinflammatory cytokines, and antiapoptotic proteins. Constitutive activation of NF‐κB in the nucleus is observed in some hematologic disorders. With the recent approval of bortezomib for patients with advanced multiple myeloma, NF‐κB modulation is likely to be a therapeutic endeavor of increasing interest in coming years. Cancer 2004. © 2004 American Cancer Society.