NF-kappaB as a prognostic marker and therapeutic target in chronic lymphocytic leukemia.
Chronic lymphocytic leukemia is the most common adult leukemia and is currently incurable with conventional chemotherapeutic agents. Over the last few years, significant discoveries have been made regarding the biology that underpins this disease. These new insights have allowed us to develop more rational prognostic tools and identify promising novel therapeutic targets. In this review, we highlight the importance of both constitutive and inducible DNA binding of the transcription factor NF-kappaB in chronic lymphocytic leukemia. We describe the current knowledge regarding the activity and function of specific NF-kappaB subunits in this disease, and discuss the complex mechanisms that regulate NF-kappaB activation in vivo. In addition, we provide compelling evidence for the utility of the NF-kappaB subunit, Rel A, as a prognostic marker and as a therapeutic target in this disease, and we also describe how this protein may contribute to the drug resistance commonly encountered with this condition.
Pepper
Chris
C
School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK. peppercj@cf.ac.uk
Hewamana
Saman
S
Brennan
Paul
P
Fegan
Chris
C
D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011379:Prognosis
D014408:Biomarkers, Tumor; D016328:NF-kappa B