Gene Expression Profiling of B Cell Chronic Lymphocytic Leukemia Reveals a Homogeneous Phenotype Related to Memory B Cells

By U. Klein, Yuhai Tu, Gustavo A. Stolovitzky, M. Mattioli, G. Cattoretti, H. Husson, A. Freedman, G. Inghirami, L. Cro, L. Baldini and 3 more. Journal of Experimental Medicine, 2001

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B cell–derived chronic lymphocytic leukemia (B-CLL) represents a common malignancy whose cell derivation and pathogenesis are unknown. Recent studies have shown that >50% of CLLs display hypermutated immunoglobulin variable region (IgV) sequences and a more favorable prognosis, suggesting that they may represent a distinct subset of CLLs which have transited through germinal centers (GCs), the physiologic site of IgV hypermutation. To further investigate the phenotype of CLLs, their cellular derivation and their relationship to normal B cells, we have analyzed their gene expression profiles using oligonucleotide-based DNA chip microarrays representative of ∼12,000 genes. The results show that CLLs display a common and characteristic gene expression profile that is largely independent of their IgV genotype. Nevertheless, a restricted number of genes (<30) have been identified whose differential expression can distinguish IgV mutated versus unmutated cases and identify them in independent panels of cases. Comparison of CLL profiles with those of purified normal B cell subpopulations indicates that the common CLL profile is more related to memory B cells than to those derived from naive B cells, CD5+ B cells, and GC centroblasts and centrocytes. Finally, this analysis has identified a subset of genes specifically expressed by CLL cells of potential pathogenetic and clinical relevance.

Subfields: Genetics, Immunology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/5125d31d37e32fd4aa48ace7a0668a569686136d

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Citations in the corpus

ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. (2003, background): “The combined use of gene expression profiling and IgVH sequencing led to the proposal that CLL is a single disease with two common variants, Ig-unmutated and Igmutated CLL.(12,13) The present analysis is in broad agreement with this view, but the ZAP-70 outlier patients suggest that CLL cannot be ne”
Reverse engineering of regulatory networks in human B cells (2005, methodology): “The gene-expression profiles data set (336 samples) includes normal purified cord blood (5 samples”
Spectral biclustering of microarray data: coclustering genes and conditions. (2003, methodology): “Unsupervised methods have been successful in separating certain types of tumors associated with different types of leukemia and lymphoma (Golub et al. 1999; Alizadeh et al. 2000; Klein et al. 2001).”
Key Issues in Conducting a Meta-Analysis of Gene Expression Microarray Datasets (2008, background): “(2001) [99] B cells 11733577 20 32 HGU95A 12,626 12,110 13,145 9,391”
Reverse engineering cellular networks (2006, methodology): “Anticipated results ARACNE has been used to study the transcriptional network associated with the MYC proto-oncogene using a data set of Affymetrix HG-U95A microarrays performed on human B lymphocytes derived from normal, tumor-related and experimentally manipulated population”
Mechanisms of B-cell lymphoma pathogenesis (2005, background): “MALT lymphoma API2–MALT1 (30)135, CD95 (5-80)25,140,141‡ Indirect role of – BCL10–IgH (5)136,137, Helicobactor pylori in MALT1–IgH (15-20)138, gastric MALT FOXP1–IgH (10)139 lymphomas85”
The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. (2010, background): “The disease is characterized by the clonal expansion of B cells that express the CD5 cell surface antigen and that are thought to derive from antigenexperienced marginal zone B cells (Chiorazzi and Ferrarini, 2003; Klein et al., 2001).”
ARACNE: An Algorithm for the Reconstruction of Gene Regulatory Networks in a Mammalian Cellular Context (2004, methodology): “To this end, we have assembled an expression profile dataset consisting of about 340 B lymphocytes derived from normal, tumor-related, and experimentally manipulated populations (for an extensive description see [28]).”
Role of Bruton’s tyrosine kinase in B cells and malignancies (2018, result): “Although initial gene expression profiling indicated that M-CLL and U-CLL were quite homogeneous and related to memory B cells derived from T cell-dependent and T-cell independent responses, respectively [123], more recent gene expression profiling studies have provided evidence for a different orig”