Nicht erst seit dem Diskursereignis um die Kölner Silvesternacht findet im öffentlichen, medialen, politischen und wissenschaftlichen Raum eine affektbesetzte Auseinandersetzung mit Gefahren und ...Bedrohungen in der Migrationsgesellschaft statt. Dabei wird von einer vermeintlichen Rückständigkeit und Gefährlichkeit derjenigen ausgegangen, die als »Andere« gelten. In den Diskursen werden ihr Wesen und Körper fokussiert, sodass sich eine Grundlage für die zunehmende Legitimation ihrer Überwachung und Bestrafung ausbildet. Die Beiträger*innen des Bandes diskutieren diese europäischen und »westlichen« Praktiken der geschlechterpolitischen Behauptung, Visualisierung und Hervorhebung migrantisierter Anderer und machen ihre Konsequenzen in unterschiedlichen Räumen deutlich.
Wer über Transferprozesse des Wissens bei enzyklopädischen Werken spricht, wird sich über kurz oder lang mit den ‚entangled histories‘ der aufgeklärten Universallexika Europas zu beschäftigen haben. ...Die zu Beginn des Zeitalters der aufgeklärten Enzyklopädien herrschenden Produktionsweise solcher Werke bedingte bereits die inhaltliche Verflechtung der jeweils jüngsten landessprachlichen Enzyklopädie mit ihren Vorläufern; sie geschah auf dem Wege des eigentlich unerlaubten, aber üblichen Nachdrucks, sie kam im Zuge der Sprachübersetzung zustande, die auch eine kulturelle war, sie bestand in den kompilatorischen Textcollagen innerhalb der Lemmata.Obwohl die Herausgeber und Autoren der landessprachlichen Enzyklopädien auf den Titelblättern beständig die Verbundenheit des neuen Werkes mit den Vorgänger-Wörterbüchern betonten, war die inhaltliche Verflochtenheit der enzyklopädischen Projekte bei gleichzeitiger ‚nationaler‘ Differenz keine offensichtliche. Sie war, wie sich an der Moréri-„Familie“ mit ihren deutschen, schweizerischen, niederländischen, englischen etc. Übersetzungen zeigen läßt, vielmehr ein verborgenes Wurzelgeflecht mit stetig neuen Ablegern. Die Übersetzung bereits existierender Enzyklopädien in verschiedene Landessprachen war von der ausschnittsweisen Revision und einer unterschiedlich starken ‚nationalen‘ Adaption der Inhalte geprägt. Eine Rückübersetzung in die Originalsprache hätte nicht eine Rückkehr zum Original bedeutet – Adaption, Revision und Anreicherung der Artikel hatten ein neues Buch und neue Wissenswirklichkeit erzeugt.
Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin's lymphoma. However, little is known regarding epigenetic similarities between cells of ...classical Hodgkin's lymphoma and plasma cell myeloma, both of which share extinction of the gene expression program of mature B cells.
Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin's lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA polymerase chain reaction for selected genes. Epigenetic modifications were compared to gene expression data.
Characteristic B-cell genes were hypoacetylated in classical Hodgkin's lymphoma and plasma cell myeloma cell lines as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin' lymphoma and plasma cell myeloma cell lines, such as IRF4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected characteristic B-cell genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin's lymphoma than in plasma cell myeloma.
Our epigenetic data support the view that classical Hodgkin's lymphoma is characterized by abortive plasma cell differentiation with a down-regulation of characteristic B-cell genes but without activation of most genes typical of plasma cells.
Summary
Sporadic Burkitt lymphoma (BL) is the most frequent tumour of children and adolescents but a rare subtype of lymphomas in adults. To date most molecular data have been obtained from lymphomas ...arising in the young. Recently, Epstein–Barr virus (EBV) positive and negative BL in young patients was shown to differ in molecular features. In the present study, we present a large age‐overarching cohort of sporadic BL (n = 162) analysed by immunohistochemistry, translocations of MYC proto‐oncogene, basic helix‐loop‐helix transcription factor (MYC), B‐cell leukaemia/lymphoma 2 (BCL2) and B‐cell leukaemia/lymphoma 6 (BCL6) and by targeted sequencing. We illustrate an age‐associated inter‐tumoral molecular heterogeneity in this disease. Mutations affecting inhibitor of DNA binding 3, HLH protein (ID3), transcription factor 3 (TCF3) and cyclin D3 (CCND3), which are highly recurrent in paediatric BL, and expression of sex determining region Y‐box transcription factor 11 (SOX11) declined with patient age at diagnosis (P = 0·0204 and P = 0·0197 respectively). In contrast, EBV was more frequently detected in adult patients (P = 0·0262). Irrespective of age, EBV‐positive sporadic BL showed significantly less frequent mutations in ID3/TCF3/CCND3 (P = 0·0088) but more often mutations of G protein subunit alpha 13 (GNA13; P = 0·0368) and forkhead box O1 (FOXO1; P = 0·0044) compared to EBV‐negative tumours. Our findings suggest that among sporadic BL an EBV‐positive subgroup of lymphomas increases with patient age that shows distinct pathogenic features reminiscent of EBV‐positive endemic BL.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Similar to resting mature B cells, where the B-cell antigen receptor (BCR) controls cellular survival, surface BCR expression is conserved in most mature B-cell lymphomas. The identification of ...activating BCR mutations and the growth disadvantage upon BCR knockdown of cells of certain lymphoma entities has led to the view that BCR signalling is required for tumour cell survival. Consequently, the BCR signalling machinery has become an established target in the therapy of B-cell malignancies. Here we study the effects of BCR ablation on MYC-driven mouse B-cell lymphomas and compare them with observations in human Burkitt lymphoma. Whereas BCR ablation does not, per se, significantly affect lymphoma growth, BCR-negative (BCR
) tumour cells rapidly disappear in the presence of their BCR-expressing (BCR
) counterparts in vitro and in vivo. This requires neither cellular contact nor factors released by BCR
tumour cells. Instead, BCR loss induces the rewiring of central carbon metabolism, increasing the sensitivity of receptor-less lymphoma cells to nutrient restriction. The BCR attenuates glycogen synthase kinase 3 beta (GSK3β) activity to support MYC-controlled gene expression. BCR
tumour cells exhibit increased GSK3β activity and are rescued from their competitive growth disadvantage by GSK3β inhibition. BCR
lymphoma variants that restore competitive fitness normalize GSK3β activity after constitutive activation of the MAPK pathway, commonly through Ras mutations. Similarly, in Burkitt lymphoma, activating RAS mutations may propagate immunoglobulin-crippled tumour cells, which usually represent a minority of the tumour bulk. Thus, while BCR expression enhances lymphoma cell fitness, BCR-targeted therapies may profit from combinations with drugs targeting BCR
tumour cells.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Die autobiographisch unterlegten Antikriegsromane von Alexander Moritz Frey (1881–1957)
(1929) und Adrienne Thomas
.
(1930) literarisieren den Erfahrungsraum des Sanitätsdienstes und der ...Kriegskrankenpflege; sie kamen in der Weimarer Republik fast gleichzeitig mit Erich Maria Remarques Bestseller
auf den Buchmarkt – und mussten diesem dank ihrer Qualität zunächst nicht weichen. Ihre Schutzumschläge und Bucheinbände, oft von renommierten Graphiker*innen geschaffen, kommentieren die in ihnen enthaltene Erzählung und sie illustrieren das Vergessen und Erinnern der Werke, die sie umschlossen.
Summary
T‐cell prolymphocytic leukaemia (T‐PLL) is an aggressive leukaemia. The primary genetic alteration in T‐PLL are the inv(14)(q11q32)/t(14;14)(q11;q32) leading to TRD/TRA‐TCL1A fusion, or the ...t(X;14)(q28;q11) associated with TRD/TRA‐MTCP1 fusion. However, additional cooperating abnormalities are necessary for emergence of the full neoplastic phenotype. Though the pattern of secondary chromosomal aberrations is remarkably conserved, targets of the changes are largely unknown. We analysed a cohort of 43 well‐characterized T‐PLL for hotspot mutations in the genes JAK3, STAT5B and RHOA. Additionally, we selected a subset of 23 T‐PLL cases for mutational screening of 54 genes known to be recurrently mutated in T‐cell and other haematological neoplasms. Activating mutations in the investigated regions of the JAK3 and STAT5B genes were detected in 30% (13/43) and 21% (8/39) of the cases, respectively, and were mutually exclusive. Further, we identified mutations in the genes encoding the epigenetic regulators EZH2 in 13% (3/23), TET2 in 17% (4/23) and BCOR in 9% (2/23) of the cases. We confirmed that the JAK‐STAT pathway is a major mutational target, and identified epigenetic regulators recurrently mutated in T‐PLL. These findings complement the mutational spectrum of secondary aberrations in T‐PLL and underscore the potential therapeutical relevance of epigenetic regulators in T‐PLL.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The incidence of diffuse large B-cell lymphoma (DLBCL) increases with age being patient age at diagnosis an adverse prognostic factor. However, elderly patients are often underrepresented in common ...studies. To investigate the effect between age and biological characteristics in DLBCL, we analyzed data of 1534 patients encompassing all adult age groups, enriched for the age ≥75 years. Follicular lymphoma (FL) grade 3B with histopathological characteristics of DLBCLs were included. Gender, centroblastic cytology, FL grade 3B morphology, CD10 expression, and ABC/non-GCB-subtype were significantly associated with age after correction for multiple testing and after adjusting for cohorts. Analysis of a subgroup points towards an association of MYC expression with age. Our data indicate that biological features of DLBCL and FL grade 3B are associated with increasing age among adult patients. The prevalence of the ABC/non-GCB-subtype in elderly patients suggests that therapies targeting this molecular subtype should be specifically explored in this subgroup.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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