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Updated: Jul 13, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia
A Rosenwald1, A A Alizadeh, G Widhopf
1Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Insights
Chronic lymphocytic leukemia (CLL) shares a common gene expression signature, indicating a unified origin. However, gene expression differences correlate with immunoglobulin mutation status, aiding in patient classification.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- B cell chronic lymphocytic leukemia (CLL) is the most common human leukemia.
- CLL exhibits a variable clinical course despite a characteristic presentation.
- CLL cells have rearranged immunoglobulin (Ig) genes that are either germ-line or somatically mutated.
Purpose of the Study:
- To investigate the molecular underpinnings of CLL heterogeneity.
- To determine if CLL comprises distinct disease entities based on Ig mutational status.
- To identify a common mechanism of transformation or cell of origin in CLL.
Main Methods:
- Genomic-scale gene expression profiling of CLL cells.
- Analysis of gene expression patterns in relation to Ig mutational status.
- Development of a CLL subtype predictor based on gene expression data.
Main Results:
- A common gene expression signature was identified across all CLL cases, irrespective of Ig mutational status.
- Hundreds of genes showed expression levels that correlated with Ig mutational status.
- These differentially expressed genes are involved in B cell receptor signaling pathways.
Conclusions:
- CLL appears to share a common transformation mechanism or cell of origin.
- Ig mutational status is associated with distinct molecular subtypes within CLL.
- A gene expression-based predictor may improve clinical classification and patient management in CLL.
Abstract:
The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease.
