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Variability in the Degree of Expression of Phosphorylated IκBα in Chronic Lymphocytic Leukemia Cases With Nodal Involvement
- Source :
- Clinical Cancer Research. 10:6796-6806
- Publication Year :
- 2004
- Publisher :
- American Association for Cancer Research (AACR), 2004.
-
Abstract
- Purpose: Based on previous preliminary observations, we hypothesize that the molecular and clinical variability of chronic lymphocytic leukemia (CLL) reflects differences in the degree of nuclear factor (NF)-κB activation, as determined by the expression of phosphorylated IκBα (p-IκBα).Experimental Design: The expression profile (mRNA and protein expression) was analyzed with the Centro Nacional de Investigaciones Oncológicas Oncochip, a cDNA microarray containing 6386 cancer-related genes, and a tissue microarray (TMA). The results were correlated with the IgVH mutational status, ZAP-70 expression, cytogenetic alterations, and clinical outcome.Results: We found correlations between the presence of p-IκBα, a surrogate marker of NF-κB activation, and changes in the expression profile (mRNA and protein expression) and clinical outcome in a series of CLL cases with lymph node involvement. Activation of NF-κB, as determined by the expression of p-IκBα, was associated with the expression of a set of genes comprising key genes involved in the control of B-cell receptor signaling, signal transduction, and apoptosis, including SYK, LYN, BCL2, CCR7, BTK, PIK3CD, and others. Cases with increased expression of p-IκBα showed longer overall survival than cases with lower expression. A Cox regression model was derived to estimate some parameters of prognostic interest: IgVH mutational status, ZAP-70, and p-IκBα expression. The multivariate analysis disclosed p-IκBα and ZAP-70 expression as independent prognostic factors of survival.Conclusions: A variable degree of activation of NF-κB, as determined by the expression of p-IκBα, is an identifiable event in CLL, and is correlated with changes in the expression profile and overall survival.
- Subjects :
- Adult
Male
Cancer Research
Microarray
Chronic lymphocytic leukemia
Syk
Biology
NF-KappaB Inhibitor alpha
LYN
Gene expression
medicine
Humans
RNA, Messenger
Phosphorylation
Aged
Oligonucleotide Array Sequence Analysis
Tissue microarray
Gene Expression Profiling
Middle Aged
Prognosis
medicine.disease
Leukemia, Lymphocytic, Chronic, B-Cell
Survival Analysis
IκBα
Oncology
Immunology
Cancer research
Female
I-kappa B Proteins
Lymph Nodes
Signal transduction
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....c8f0ddef9f7ed84eeb09c0553642ec87