Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma

By Andreas Rosenwald, George W. Wright, K. Leroy, Xin-You Yu, P. Gaulard, R. Gascoyne, W. Chan, T. Zhao, C. Haioun, T. Greiner and 28 more. Journal of Experimental Medicine, 2003

1,127 citations recorded by the source corpus.

Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.

Subfields: Gastroenterology, Genetics, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/d6bb84fe3288d8fc8545f870be81a82755b6058e

How researchers see this paper

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In Genetics

1. Ralf Küppers
2. R. Dalla-Favera
3. U. Klein
4. D. Calado
5. J. Fishman

In Pathology and Forensic Medicine

1. Ralf Küppers
2. R. Dalla-Favera
3. U. Klein
4. D. Pardoll
5. D. Calado
6. J. Fishman

Citations in the corpus

• The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. (2011, background): “GEP studies further revealed that PMBCL and CHL share a common gene expression signature, supporting a close biological relationship.(96;97)”
• PD-1 and its ligands in tolerance and immunity. (2008, background): “PD-1 or PDL1 are rarely expressed on B cell malignancies (55), but PD-L2 has been identified by microarray analysis as being highly expressed in mantle cell lymphomas (132).”
• Analysis of the Coding Genome of Diffuse Large B-Cell Lymphoma (2011, background): “Current understanding of the biology of DLBCL indicates the existence of several disease subgroups reflecting the derivation from B cells at discrete stages of differentiation, namely germinal-center B-cell–like (GCB) DLBCL, activated B-cell–like (ABC) DLBCL and primary mediastinal B-cell lymphoma (”
• Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways (2008, neutral): “This MCR has been reported previously to occur in both PMBL and Hodgkin’s lymphoma (6, 29), 2 lymphomas that share a common gene-expression signature, clinical presentation in younger patients, and possible origin from thymic B cells (6, 7).”
• A New Immunostain Algorithm Classifies Diffuse Large B-Cell Lymphoma into Molecular Subtypes with High Accuracy (2009, neutral): “On examination of GEP data, GCET1, GCET2, and MTA3 showed high GC specificity but LIM domain only 2 was less specific (7), although its protein expression by IHC was reported to be more GC-specific and also associated with significantly better survival (19, 36).”
• The blockade of immune checkpoints in cancer immunotherapy (2012, background): “PDL2 is highly upregulated on cells from certain B cell lymphomas, such as primary mediastinal B cell lymphoma, follicular cell B cell lymphoma and Hodgkin's diseas”
• 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”
• BIC and miR‐155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas (2005, neutral): “Several studies have reported a close relationship between HL and PMBL cases, based on similar gene expression profiles and common genomic aberrations [ 27 ,28].”
• The 2008 WHO classification of lymphomas: implications for clinical practice and translational research (2009, neutral): “The use of gene expression profiling further confirmed a biological relationship.(35,36) Prior case reports had identified cases of PMBL followed by CHL or vice versa, or other cases in which both lymphomas were composite in the same tumor mass.”
• Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity (2012, neutral): “In lymphoid malignancies, B7-DC/ PD-L2 is more commonly up-regulated [27], likely in response to different set of proinflammatory cytokine signals.”
• Transcription factor IRF4 controls plasma cell differentiation and class-switch recombination (2006, background): “and is often abnormally expressed in B cell lymphoma”