Tumor necrosis factor receptor-associated factor 1 gene overexpression in B-cell chronic lymphocytic leukemia: analysis of NF-kappa B/Rel-regulated inhibitors of apoptosis.
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a resistance toward apoptosis-inducing agents. Nuclear factor-kappaB (NF-kappaB)/Rel has been shown to regulate the expression of antiapoptotic genes, such as members of the inhibitor of apoptosis protein (IAP) and tumor necrosis factor receptor-associated factor (TRAF) gene families. Expression and regulation of NF-kappaB/Rel-dependent ... inhibitors of apoptosis have not been collectively studied in B-CLL. We examined expression of known NF-kappaB/Rel-regulated antiapoptotic genes by RNAse protection assay, real-time polymerase chain reaction, and immunoblotting in patients with B-CLL. TRAF1 and to a lesser extent TRAF2 were overexpressed in B-CLL lymphocytes as compared with normal CD19(+) B cells. TRAF1 overexpression did not correlate with markers of disease progression or overall survival. Furthermore, we found high constitutive expression of the IAP genes c-IAP-1, c-IAP-2, and XIAP both in normal and B-CLL lymphocytes. Focusing on the regulation of TRAF1, NF-kappaB/Rel activity in B-CLL nuclear extracts was shown to bind to TRAF1 promoter elements. However, IkappaB kinase (IKK) activity was not increased in CLL lymphocytes as compared with normal CD19(+) B cells. The known IKK inhibitor sulfasalazine did not compromise TRAF1 expression. Thus, although our study revealed a common expression pattern of NF-kappaB/Rel-regulated inhibitors of apoptosis, our findings indicate an IKK-independent regulation of TRAF1 in B-CLL.
Mesh Terms:
Adult, Aged, Aged, 80 and over, Apoptosis, Autocrine Communication, Case-Control Studies, Gene Expression Regulation, Neoplastic, Humans, I-kappa B Kinase, Inhibitor of Apoptosis Proteins, Insect Proteins, Leukemia, Lymphocytic, Chronic, B-Cell, Middle Aged, NF-kappa B, Neoplasm Proteins, Oncogene Proteins v-rel, Protein-Serine-Threonine Kinases, Proteins, RNA, Messenger, TNF Receptor-Associated Factor 1, Up-Regulation
Adult, Aged, Aged, 80 and over, Apoptosis, Autocrine Communication, Case-Control Studies, Gene Expression Regulation, Neoplastic, Humans, I-kappa B Kinase, Inhibitor of Apoptosis Proteins, Insect Proteins, Leukemia, Lymphocytic, Chronic, B-Cell, Middle Aged, NF-kappa B, Neoplasm Proteins, Oncogene Proteins v-rel, Protein-Serine-Threonine Kinases, Proteins, RNA, Messenger, TNF Receptor-Associated Factor 1, Up-Regulation
Blood
Date: Nov. 15, 2002
PubMed ID: 12411322
View in: Pubmed Google Scholar
Download Curated Data For This Publication
143078
Switch View:
- Interactions 2