Nuclear factor-kappaB modulation as a therapeutic approach in hematologic malignancies.
Nuclear factor-kappaB (NF-kappaB) 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-kappaB proteins promote transcription, some act as inactivating or repressive complexes. The most common p50-RelA (p65) dimer known "specifically" as NF-kappaB, is relatively abundant, controls the expression of numerous genes, and exists as an inactive cytoplasmic complex bound to inhibitory proteins of the NF-kappaB inhibitor (IkappaB) family. The inactive NF-kappaB-IkappaB complex is activated by a variety of stimuli, including proinflammatory cytokines, mitogens, growth factors, and stress-inducing agents. The release of NF-kappaB 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-kappaB in the nucleus is observed in some hematologic disorders. With the recent approval of bortezomib for patients with advanced multiple myeloma, NF-kappaB modulation is likely to be a therapeutic endeavor of increasing interest in coming years.
Panwalkar
Amit
A
Section of Developmental Therapeutics, Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Verstovsek
Srdan
S
Giles
Francis
F
D002453:Cell Cycle / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D019008:Drug Resistance, Neoplasm; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D016328:NF-kappa B / Q000494:pharmacology* / Q000627:therapeutic use*; D015398:Signal Transduction
D016328:NF-kappa B