@article{RitterZimmermannJoehrensetal.2018,
  author    = {Ritter, Julia and Zimmermann, Karin and J{\"o}hrens, Korinna and Mende, Stefanie and Seegebarth, Anke and Siegmund, Britta and Hennig, Steffen and Todorova, Kremena and Rosenwald, Andreas and Daum, Severin and Hummel, Michael and Schumann, Michael},
  title     = {T-cell repertoires in refractory coeliac disease},
  series = {Gut},
  volume    = {67},
  journal   = {Gut},
  number    = {4},
  doi       = {10.1136/gutjnl-2016-311816},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226350},
  pages     = {644-653},
  year      = {2018},
  abstract  = {Objective Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis. Design DNA extracted from duodenal mucosa specimens of controls (n=9), active coeliacs (n=10), coeliacs on a gluten-free diet (n=9), RCD type I (n= 8), RCD type II (n= 8) and unclassified Marsh I cases (n= 3) collected from 2002 to 2013 was examined by TCR beta-complementarity- determining regions 3 (CDR3) multiplex PCR followed by HTS of the amplicons. Results On average, 106 sequence reads per sample were generated consisting of up to 900 individual TCR beta rearrangements. In RCD type II, the most frequent clonotypes (ie, sequence reads with identical CDR3) represent in average 42.6\% of all TCR beta rearrangements, which was significantly higher than in controls (6.8\%; p<0.01) or RCD type I (6.7\%; p<0.01). Repeat endoscopies in individual patients revealed stability of clonotypes for up to several years without clinical symptoms of EATL. Dominant clonotypes identified in individual patients with RCD type II were unique and not related between patients. CD-associated, gliad-independent CDR3 motifs were only detectable at low frequencies. Conclusions TCR beta-HTS analysis unravels the TCR in CD and allows detailed analysis of individual TCR beta rearrangements. Dominant TCR beta sequences identified in patients with RCD type II are unique and not homologous to known gliadin-specific TCR sequences, supporting the assumption that these clonal T-cells expand independent of gluten stimulation.},
  language  = {en}
}
@phdthesis{Andrulis2005,
  author    = {Andrulis, Mindaugas},
  title     = {BLIMP1 Expression in diffusen großzelligen B-Zell Lymphomen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-17877},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {BLIMP1 ist ein Transkriptionsfaktor und Schl{\"u}sselregulator in der Plasmazell-Differenzierung. Um die Rolle des BLIMP1 in der Lymphomentstehung zu untersuchen, wurde die BLIMP1 Expression im normalen humanen lymphatischen Gewebe und in 78 diffusen großzelligen B-Zell Lymphomen untersucht. BLIMP1 wurde in Plasmazellen und GC B-Zellen sowie in einer Population extrafollikul{\"a}rer B-Zellen exprimiert. Die reifen Plasmazellen vom Marschalko-Typ waren CD138+CD20-MUM1+Ki67-BCL6-PAX5-BLIMP1+. Außerdem zeigten die Keimzentrums-B-Zellen keine Ki67-Expression. Im Gegensatz hierzu waren die BLIMP1+ EGBZ Ki67+p27-. BLIMP1 wurde in 19\% (15/78) der DLBCL F{\"a}lle, darunter ABC- (7/15) und GCB- (8/15) Typ, exprimiert. BLIMP1+ DLBCL konnten entsprechend dem BLIMP1, BCL6 und PAX5 Expressionsprofil in drei pathogenetisch unterschiedliche Typen unterteilt werden. In den Typ A-F{\"a}llen waren die BLIMP1+ Tumor- zellen st{\"a}ndig BCL6-/PAX5- und waren alle vom ABC-Typ (CD10-/BCL6-/MUM1+). Im Typ B-DLBCL waren die meisten Tumorzellen st{\"a}ndig BLIMP1-/BCL6+/PAX5+ und BLIMP1 war nur in relativ kleinen Arealen herdf{\"o}rmig exprimiert. Die BLIMP1+ Zellen zeigten keine BCL6 und PAX5 Expression, und alle Typ B-F{\"a}lle zeigten ein GCB-Profil (CD10+ oder BCL6+ und MUM1-). Die Typ C-F{\"a}lle waren durch eine gleichzeitige BLIMP1 und BCL6 und/oder PAX5 Expression gekennzeichnet, was einem ab{\"a}rranten und nicht in normalen B-Zellen auftretenden Immunph{\"a}notyp entspricht. Weiterhin wurden in 7 F{\"a}llen mit Allelverluste auf der Genomregion 6q21, der das BLIMP1 Gen enth{\"a}lt, keine BLIMP1 Mutationen gefunden. Hinsichtlich einer BLIMP1 Expression im normalen lymphatischen Gewebe konnte festgestellt werden, dass das BLIMP1 nicht nur w{\"a}hrend der Plasmazellentwicklung aus den Keimzentrums-B-Zellen eine bedeutende Rolle spielt, sondern auch mit der Plasmazell-Differenzierung außerhalb des Keimzentrums assoziiert ist. Eine BLIMP1 Expression in DLBCL kennzeichnet die F{\"a}lle mit einer Plasmazell-Differenzierung. BLIMP1 ist in den Lymphomen gr{\"o}ßtenteils wie in normalen B-Zellen reguliert und besitzt die Kapazit{\"a}t, die Plasmazell-Entwicklung in die Tumorzellen zu induzieren. Jedoch reicht die BLIMP1 Expression weder aus, den Zellzyklus aufzuhalten, noch eine komplette terminale Plasmazell-Reifung in den DLBCL zu leiten. Allerdings scheint BLIMP1 nicht von den bekannten TSG Inaktivierungsmechanismen in den DLBCL betroffen zu sein, wobei es sehr unwahrscheinlich ist, dass das BLIMP1 ein TSG darstellt, dessen Verlust bei der Lymphomentwicklung eine wesentliche Rolle spielt.},
  language  = {de}
}
@phdthesis{Akimzhanov2005,
  author    = {Akimzhanov, Askar M.},
  title     = {Epigenetic repression of the NFATc1 transcription factor in human lymphomas},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-12921},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {We examined the regulation of NFATc1 in different lymphomas and observed an inversed correlation between the methylation status and expression of NFATc1. Our data demonstrate that aberrant DNA methylation associated with chromatin remodeling within nfatc1 locus is a major mechanism for the repression of NFATc1 expression, suggesting that the DNA methylation-mediated transcriptional silencing of NFATc1 may be a critical event in the tumorogenesis of ALCLs and cHLs. Furthermore, the DNA methylation of human nfatc1 promoter region could be used as a novel biomarker of tumor progression. Our results indicate a close link between the loss of immunoreceptor signaling and NFATc1 expression in human lymphomas. For both ALCLs and cHLs, defects in immunoreceptor signaling have been described which result in a loss of receptor-mediated gene expression programs (Schwering et al., 2003; Bonzheim et al., 2004; Marafioti et al., 2004). In T cells, one indicator gene of these programs appears to be the nfatc1 gene whose expression is controlled by TCR signals (Chuvpilo et al., 2002a). In contrast, in T cells NFATc1 expression is unaffected by TCR signals, and NFATc2 was found to be expressed at normal levels in ALCLs and cHLs (L.K., unpubl. data). Moreover, the activity of NF-kappaB factors which can bind to certain NFAT binding sites and share a distantly-related DNA binding domain with NFATs is strongly elevated in cHL cells (Bargou et al., 1997; Hinz et al., 2001; Hinz et al., 2002) suggesting that NFATs and NF-kappaBs exert very different effects on generation and maintenance of Hodgkin's lymhomas. However, it should be mentioned that in Burkitt's and further B cell lymphomas in which NFATc1 proteins are strongly expressed and controlled by receptor signals (Kondo et al., 2003), they could exert a promoting function in tumor development. The genes of p53 family members p63 and p73 are prominent examples for mammalian genes whose products can act both as oncoproteins and tumor suppressor genes (Hibi et al., 2000; Stiewe and Putzer, 2002), and it is likely that more genes exist which encode both tumor suppressors and oncoproteins. It remains to be shown whether the nfatc1 gene is one of them.},
  subject      = {Lymphom},
  language  = {en}
}