Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma

Steidl, Christian; Diepstra, Arjan; Lee, Tang; Chan, Fong Chun; Farinha, Pedro; Tan, King; Telenius, Adèle; Barclay, Lorena; Shah, Sohrab P.; Connors, Joseph M.; Berg, Anke van den; Gascoyne, Randy D.

doi:10.1182/blood-2012-06-439570

Cited by 133 publications

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“…Remarkably, we 5 also found a prominent enrichment of clusters related to inflammatory processes, such as cytokine production and activity, receptor-ligand or cell-cell interactions and lymphocyte activation (Supplementary Table 3 Table 5), but are also prominent components of deregulated functional pathways in HRS cells. 14,15 As a major feature of the cellular response to IL-15 stimulation, we identified a significant induction of cytokines and chemokines in HRS cells. Several of these factors, such as IL-6, IL-9 and CCL3, in turn may have the potential to mediate growth and survival signals for HRS cells as well as to attract or stimulate cells of the tumor microenvironment.…”

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confidence: 91%

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confidence: 99%

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The IL-15 cytokine system provides growth and survival signals in Hodgkin lymphoma and enhances the inflammatory phenotype of HRS cells

et al. 2014

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Gene expression profiles of KM-H2 cells were determined at 0, 4, 10 and 24 hours of rhIL-15 treatment and normalized to profiles of PBS-treated KM-H2 cells that were analyzed in parallel to control for expression changes induced by growth in cell culture per se. This approach identified a specific set of genes that showed a significant regulation by rhIL-15 at the respective time points, with 43 genes being differentially expressed at 24 hours (with a fold change of at least log2 0.75 ; Supplementary Table 2). To identify biological processes regulated by IL-15, we used the DAVID classification tool that classifies gene lists into functionally related gene groups. In accordance with our functional data, we observed a significant enrichment of gene ontology (GO) terms associated with cellular proliferation and survival within our set of rhIL-15-regulated genes (Supplementary Table 3). Remarkably, we 5 also found a prominent enrichment of clusters related to inflammatory processes, such as cytokine production and activity, receptor-ligand or cell-cell interactions and lymphocyte activation (Supplementary Table 3 Table 5), but are also prominent components of deregulated functional pathways in HRS cells. 14,15 As a major feature of the cellular response to IL-15 stimulation, we identified a significant induction of cytokines and chemokines in HRS cells. Several of these factors, such as IL-6, IL-9 and CCL3, in turn may have the potential to mediate growth and survival signals for HRS cells as well as to attract or stimulate cells of the tumor microenvironment. 1,2 In summary, our study identifies IL-15 as part of the complex interactions between tumor cells and the microenvironment in HL that provides growth and survival signals for HRS cells.6

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confidence: 91%

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confidence: 99%

The IL-15 cytokine system provides growth and survival signals in Hodgkin lymphoma and enhances the inflammatory phenotype of HRS cells

et al. 2014

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“…Moreover, Hodgkin and Reed-Sternberg cells are known to express several additional markers usually expressed by antigenpresenting cells. [46][47][48] Although Hodgkin and ReedSternberg cells have usually lost their B-cell phenotype, they have maintained the features for an interaction with T cells, which is not observed in the tumor cells of ALK À anaplastic large cell lymphoma. Interestingly, Hodgkin lymphoma cases with granzyme B expression were less frequently positive for MDC/CCL22 and CD83 than conventional classical Hodgkin lymphoma cases.…”

Section: Discussionmentioning

confidence: 99%

A novel immunohistochemical classifier to distinguish Hodgkin lymphoma from ALK anaplastic large cell lymphoma

et al. 2014

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Classical Hodgkin lymphoma and ALK À anaplastic large cell lymphoma share many features like strong CD30 expression and usually loss of B-and T-cell markers. However, their clinical course is dramatically different with curability rates of 490% for classical Hodgkin lymphoma and an unfavorable prognosis for anaplastic large cell lymphoma. Classical Hodgkin lymphoma and ALK À anaplastic large cell lymphoma can usually be distinguished by PAX5 expression in the Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma and expression of cytotoxic molecules in tumor cells of anaplastic large cell lymphoma. However, in some cases the differential diagnosis is difficult owing to absence of established markers. To be able to better classify these cases, we reevaluated gene expression data of microdissected tumor cells of both lymphomas for differentially expressed genes. A classifier was established, comprising four genes strongly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma (MDC/CCL22, CD83, STAT3, and TUBB2B). Applying this classifier to a test cohort, Hodgkin lymphoma was successfully distinguished from ALK À anaplastic large cell lymphoma with an accuracy of 97% (43/44). MDC/CCL22, CD83, and STAT3 have also been found to be expressed in antigen-presenting cells. Therefore, based on our established classifier, Hodgkin and Reed-Sternberg cells differ from tumor cells of anaplastic large cell lymphoma, which can successfully be applied for practical purposes in histopathologic diagnostics.

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“…In fact, molecular features of HRS cells in cHL demonstrate that they are derived from GC B cells that have acquired disadvantageous immunoglobulin variable chain gene mutations and normally would have undergone apoptosis (Kuppers et al, 2012). As shown in gene expression profiling (GEP) studies, HRS cells have lost the expression of most B-cell genes and acquired expression of genes that are typical for other types of immune cells (Greaves and Gribben 2012;Steidl et al 2012;Tiacci et al, 2012). Phenotype: Phenotypically, HRS cells of cHL are consistently positive for CD30, CD15, CD40, and IRF4/MUM1 (Stein et al, 2008).…”

Section: Phenotype/cell Stem Originmentioning

confidence: 99%

Classical Hodgkin lymphoma

Carbone¹,

Gloghini²

2018

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma

Cited by 133 publications

References 50 publications

The IL-15 cytokine system provides growth and survival signals in Hodgkin lymphoma and enhances the inflammatory phenotype of HRS cells

The IL-15 cytokine system provides growth and survival signals in Hodgkin lymphoma and enhances the inflammatory phenotype of HRS cells

A novel immunohistochemical classifier to distinguish Hodgkin lymphoma from ALK anaplastic large cell lymphoma

Classical Hodgkin lymphoma

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