NF-kappaB as a therapeutic target in chronic lymphocytic leukemia.
BACKGROUND
NF-kappaB includes a family of transcription factors that play a critical role in the biology of normal lymphocytes and it is aberrantly activated in chronic lymphocytic leukemia (CLL) cells. Here, we review the role of constitutive NF-kappaB activation in CLL pathogenesis and its potential as a therapeutic target for CLL treatment.


METHODS
This review highlights the different strategies reported to inhibit NF-kappaB signaling in CLL cells. They include both IkappaB kinase inhibitors and several natural compounds that act at different steps of the pathway.


RESULTS
Targeting NF-kappaB leads to apoptosis of CLL cells, corroborating the role of NF-kappaB in the survival and clonal expansion of these tumoral cells. Moreover, several studies confirmed a synergistic effect between NF-kappaB inhibitors and other antitumoral agents and that inhibition of NF-kappaB could overcome the microenvironmental protection of CLL cells.


CONCLUSIONS
NF-kappaB is a relevant target in CLL and inhibitors of this prosurvival pathway, alone or in combination, represent a novel therapeutic strategy for the treatment of CLL patients.
Hematopathology Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Spain.
Monica
M
Lopez-Guerra
Dolors
D
Colomer
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D004357:Drug Synergism; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000503:physiopathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D016328:NF-kappa B; D051550:I-kappa B Kinase