Relation of Gene Expression Phenotype to Immunoglobulin Mutation Genotype in B Cell Chronic Lymphocytic Leukemia

By Andreas Rosenwald, Ash A. Alizadeh, G. Widhopf, Richard M. Simon, R. Davis, Xin Yu, Liming Yang, O. Pickeral, L. Rassenti, J. Powell and 9 more. Journal of Experimental Medicine, 2001

1,219 citations recorded by the source corpus.

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.

Subfields: Genetics, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a42b58f055748853357251190730ab4167f1bf29

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In Genetics

1. G. Schulte
2. J. Petersen
3. J. Dijksterhuis

In Molecular Biology

1. G. Schulte
2. J. Petersen
3. J. Dijksterhuis
4. Louis Staudt

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, methodology): “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”
• Coexpression analysis of human genes across many microarray data sets. (2004, neutral): “…(Ramaswamy et al. 2001) 255 9528 372500 (Butte et al. 2000) 68 4906 81755 (Rickman et al. 2001) 51 5418 60169 (Chang et al. 2002) 50 13079 328274 (Rosenwald et al. 2001) 102 3751 129814 (Chaussabel et al. 2003) 28 8243 80559 (Ross and Perou 2001) 24 12437 3409 (Chen et al. 2002) 207 9169 597313…”
• INTERNATIONAL UNION OF BASIC AND CLINICAL PHARMACOLOGY REVIEW WNT/Frizzled signalling: receptor-ligand selectivity with focus on FZD-G protein signalling and its physiological relevance: IUPHAR Review 3 (2014, positive): “WNT-3A is also noted to be a ‘signature gene’ in CLL (Rosenwald et al., 2001), suggesting that this ligand/receptor pair are significantly involved with this disease.”