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Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. In the least curable (ABC) subtype of DLBCL, survival of the malignant cells is dependent on constitutive activation of the nuclear factor-kappaB (NF-kappaB) signaling pathway. In normal B cells, antigen receptor-induced NF-kappaB activation requires CARD11, a(More)
BACKGROUND Large gene expression studies, such as those conducted using DNA arrays, often provide millions of different pieces of data. To address the problem of analyzing such data, we describe a statistical method, which we have called 'gene shaving'. The method identifies subsets of genes with coherent expression patterns and large variation across(More)
The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we(More)
A role for B-cell-receptor (BCR) signalling in lymphomagenesis has been inferred by studying immunoglobulin genes in human lymphomas and by engineering mouse models, but genetic and functional evidence for its oncogenic role in human lymphomas is needed. Here we describe a form of 'chronic active' BCR signalling that is required for cell survival in the(More)
Gene-expression profiling has identified 3 major subgroups of diffuse large B-cell lymphoma (DLBCL): germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal DLBCL (PMBCL). Using comparative genomic hybridization (CGH), we investigated the genetic alterations of 224 cases of untreated DLBCL (87 GCB-DLBCL, 77 ABC-DLBCL, 19(More)
Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history re¯ects unrecognized molecular heterogeneity in the tumours.(More)
Burkitt's lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies. The normal germinal centre B cell is the presumed cell of origin for both BL and diffuse large B-cell lymphoma (DLBCL), yet gene(More)
The Leukemia and Lymphoma Molecular Profiling Project recently published results from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four gene expression "signatures" were identified as correlated with patient outcome, including the major histocompatibility complex (MHC) class II genes (eg, HLA-DRA) which correlated with better(More)
To elucidate the mechanisms underlying chromosomal translocations in diffuse large B cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used Southern blotting to detect legitimate and illegitimate CSR events in tumor samples of the activated B cell-like (ABC), germinal center B(More)
Grade 3 follicular lymphoma (FL3) is thought to have an aggressive clinical course. On the basis of possible biologic differences, the new World Health Organization (WHO) classification of lymphoma suggests further subdivision of FL3 into grades 3a and 3b and states that the percentage of involvement by diffuse large B-cell lymphoma (DLBCL) should also be(More)