Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling

  title={Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling},
  author={Ash A. Alizadeh and Michael B. Eisen and R. Eric Davis and Chishieva Ma and Izidore S. Lossos and Andreas Rosenwald and Jennifer C. Boldrick and Hajeer Sabet and T L N Tran and Xin Yu and John I. Powell and Liming Yang and Gerald Marti and Troy Moore and James I. Hudson and Li-Sheng Lu and David B. Lewis and Robert Tibshirani and Gavin Sherlock and Wing C. Chan and Timothy C Greiner and Dennis D. Weisenburger and James Olen Armitage and Roger A. Warnke and Ronald Levy and Wyndham H Wilson and Michael R Grever and John C. Byrd and David Botstein and Patrick O. Brown and Louis M. Staudt},
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. [] Key Result We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation.
Gene Expression Profiling of Diffuse Large B-Cell Lymphoma
Gene expression profiling has been used to identify individual genes that predict overall survival in DLBCL, the majority coming from gene expression signatures that reflect the cell of origin, proliferation rate, and host immune response to the tumor.
B-cell differentiation, apoptosis and proliferation in diffuse large B-cell lymphomas.
There has been accumulating molecular and immunohistochemical evidence indicating links between B-cell differentiation gene expression profiles and expression of apoptosis and cell cycle-associated genes in DLBCL.
Diffuse large B-cell lymphoma - tumour characteristics on RNA and protein level associated with prognosis
Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma subtype. In Sweden 450 new cases are diagnosed annually. With modern anthracycline-containing chemotherapy DLBCL is potentially
Novel therapeutic targets in diffuse large B-cell lymphoma
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Diffuse large B cell lymphoma: from gene expression profiling to prediction of outcome.
  • I. Lossos
  • Biology
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2008
Biological Pathways in B-cell Non-Hodgkin's Lymphoma
It was found that high expression of TCL1 was related to poor prognosis in CLL and MCL in microarray and immunohistochemistry respectively, while they also define striking heterogeneity within known lymphoma types.
Molecular Characteristics of Diffuse Large B-cell Lymphoma, Not Otherwise Specified
Gene profiling has identified “cell-of-origin” molecular subtypes of DLBCL based on expression patterns similar to normal B-cells, which will certainly impact routine diagnosis, classification, and therapeutic decisions.
Precision Treatment of Distinct Molecular Subtypes of Diffuse Large B-cell Lymphoma: Ascribing Treatment Based on the Molecular Phenotype
This work offers the chance of improving the curability of DLBCL, particularly in the activated B-cell subtype, where standard approaches are inadequate for a high proportion of patients.
The biology of human lymphoid malignancies revealed by gene expression profiling.


Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma.
Although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, B cl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs.
Clinical significance of bcl2 and p53 protein expression in diffuse large B-cell lymphoma: a population-based study.
  • M. Kramer, J. Hermans, P. Kluin
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 1996
PURPOSE We studied the prognostic significance of bcl2 and p53 protein expression in relation to clinical and pathologic characteristics in patients with diffuse large B-cell lymphoma (LCL).
Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma.
The data show the complex nature of molecular events in DLCL, which is a reflection of the morphologic and clinical heterogeneity of these lymphomas, and thus far, these genetic rearrangements fail as prognostic markers.
Clonal evolution of a follicular lymphoma: evidence for antigen selection.
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  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
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Findings indicate that antigen stimulation may be involved in the growth of follicular lymphoma tumors.
Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays.
The use of cDNA microarrays containing 1238 cDNAs to investigate the gene expression profile of a group of seven alveolar rhabdomyosarcoma (ARMS) cell lines determined that ARMS cells show a consistent pattern of gene expression, which allows the cells to be clustered together.
Molecular and immunological dissection of diffuse large B cell lymphoma: CD5+, and CD5− with CD10+ groups may constitute clinically relevant subtypes
The data suggest that the phenotypic delineation by the detection of CD5 and CD10 will improve the understanding of DLBL and be helpful in a future subgrouping ofDLBL.
The expression of BCL‐6 protein was investigated in human reactive lymphoid tissue and compared with a group of non‐Hodgkin's lymphomas with or without 3q27 anomalies and/or B CL‐6 gene rearrangement, where it was found that all follicular lymphomas tested showed a pattern of expression similar to the reactive B follicle, independently of the presence of BCR‐6 genes and/ or 3q 27 anomalies.
The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation
BCL-6 functions as a transcriptional switch that controls germinal centre formation and may also modulate specific T-cell-mediated responses and develop an inflammatory response in multiple organs typical of a Th2-mediated hyperimmune response.
The A-myb gene is preferentially expressed in tonsillar CD38+, CD39-, and sIgM- B lymphocytes and in Burkitt's lymphoma cell lines.
It is shown here, by using cell sorting, PCR, and Western analyses, that A-myb is most highly expressed in the subsets of human tonsillar B lymphocytes with the phenotypes CD38+, CD39-, and SIgM-.
Identification of Functional Human Splenic Memory B Cells by Expression of CD148 and CD27
Examining the expression of the receptor-type protein tyrosine phosphatase CD148 on human B cells identifies CD148 and CD27 as markers which positively identify memory B cells present in human spleen.