The pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly due to the technical challenge of analyzing its rare neoplastic L&H cells, which are dispersed in an abundant non-neoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected lymphocytic and histiocytic (L&H) lymphoma cells in comparison to normal and other malignant B cells, which indicates a relationship of L&H cells to and/or origin from germinal center B cells at transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell-rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype and deregulation of many apoptosis-regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive NF-B activity and aberrant ERK signaling. Thus, these findings shed new light on the nature of L&H cells, revealed several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies.
Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis.
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View SamplesAnaplastic large cell lymphoma (ALCL) is a main type of T cell lymphomas and comprises three distinct entities: systemic ALK+, systemic ALK- and cutaneous ALK- ALCL. Little is known about their pathogenesis and their cellular origin, and morphological and immunophenotypical overlap exists between ALK- ALCL and classical Hodgkin lymphoma (cHL). We conducted gene expression profiling of microdissected lymphoma cells of ALK+ and ALK- systemic ALCL, cutaneous ALCL and cHL, and of eight subsets of normal T and NK cells. The analysis supports a derivation of ALCL from activated T cells, but the lymphoma cells acquired a gene expression pattern hampering an assignment to a CD4+, CD8+ or CD30+ T cell origin. Indeed, ALCL display a general down-modulation of T cell characteristic molecules. All ALCL types show significant expression of NFB target genes and upregulation of genes involved in oncogenesis (e.g. EZH2). Surprisingly few genes are differentially expressed between systemic and cutaneous ALK- ALCL despite their different clinical behaviour, and between ALK- ALCL and cHL despite their different cellular origin. ALK+ ALCL are characterized by expression of genes regulated by pathways constitutively activated by ALK. This study provides multiple novel insights into the molecular biology and pathogenesis of ALCL.
Gene expression profiling of isolated tumour cells from anaplastic large cell lymphomas: insights into its cellular origin, pathogenesis and relation to Hodgkin lymphoma.
Specimen part
View SamplesHuman PB B cell subsets are functionally distinct and may derive from different developmental pathways, reflected by their differential gene expression profiles.
Functional capacities of human IgM memory B cells in early inflammatory responses and secondary germinal center reactions.
Specimen part
View SamplesThe role of innate immunity in modulating severity of chemotherapy-induced complications is so far unclear. The aim of this study was to determine how TLR2 may influence MTX-induced mucositis in the small intestine in mice. We used microarrays to assess gene expression profiles in proximal jejunum of WT vs. TLR2 KO mice after systemic treatment with MTX.
TLR signaling modulates side effects of anticancer therapy in the small intestine.
Specimen part, Treatment
View SamplesCommon missense mutations (D299G, T399I) have been recently identified in the human TLR4 gene. The aim of this study was to determine how TLR4 and associated mutants affect gene expression in Caco-2 cells.
No associated publication
Specimen part, Cell line
View SamplesHuman Ulcerative colitis (UC) is characterized by chronic colonic inflammation and has been associated with an increased risk of colorectal carcinoma. Gene and protein expression profiles of ABCB1/MDR1 have been shown to be dysregulated in UC and sporadic colorectal cancer. We demonstrated that in a murine model of colitis-associated tumorigenesis, MDR1A KO mice showed reduced tumor load when compared to wildtype (WT) mice. The aim of this study was to identify gene alterations in colitis-associated tumors in the context of MDR1A deficiency.
No associated publication
No sample metadata fields
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Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Specimen part
View SamplesDifferentiation of hematopoietic stem cells (HSCs) is regulated by a concert of different transcription factors (TFs). A disturbed function of TFs can be the basis of (pre)malignancies such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Growth Factor Independence 1b (Gfi1b) is a repressing TF with a key role in quiescence of HSCs and emergence and maturation of erythrocytes and platelets. Here, we show that low expression of GFI1B in blast cells is associated with inferior prognosis of MDS and AML patients. Using mouse models with either reduced expression or conditional deletion of Gfi1b, crossed with a mouse model reflecting human MDS or AML, we demonstrate that AML development was accelerated with heterozygous loss of Gfi1b, and latency was further decreased when Gfi1b was conditionally deleted. Loss of Gfi1b significantly enhanced stemness of leukemic cells with upregulation of genes fundamentally involved in leukemia development. On a molecular level, we found that loss of Gfi1b not only increased the levels of reactive oxygen species (ROS) but also induced gene expression changes of key AML pathways such as the p38/AKT pathway. These results demonstrate that Gfi1b functions as an oncosuppressor in MDS/AML development.
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression.
Specimen part
View SamplesGrowth factor independence 1b (Gfi1b) is a DNA binding repressor of transcription with vital functions in hematopoiesis. Gfi1b-null embryos die at midgestation very likely due to defects in erythro- and megakaryopoiesis. To analyze the full functionality of Gfi1b in embryonic erythropoiesis, we used conditionally deficient mice that harbor floxed Gfi1b alleles and one EpoR-Cre knock-in allele.
Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression.
Specimen part
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