@article{WongWinterHartigetal.2014,
  author    = {Wong, David and Winter, Oliver and Hartig, Christina and Siebels, Svenja and Szyska, Martin and Tiburzy, Benjamin and Meng, Lingzhang and Kulkarni, Upasana and F{\"a}hnrich, Anke and Bommert, Kurt and Bargou, Ralf and Berek, Claudia and Van, Trung Chu and Bogen, Bjarne and Jundt, Franziska and Manz, Rudolf Armin},
  title     = {Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {10},
  doi       = {10.1371/journal.pone.0109018},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115269},
  pages     = {e109018},
  year      = {2014},
  abstract  = {Multiple myeloma is a bone marrow plasma cell tumor which is supported by the external growth factors APRIL and IL-6, among others. Recently, we identified eosinophils and megakaryocytes to be functional components of the micro-environmental niches of benign bone marrow plasma cells and to be important local sources of these cytokines. Here, we investigated whether eosinophils and megakaryocytes also support the growth of tumor plasma cells in the MOPC315. BM model for multiple myeloma. As it was shown for benign plasma cells and multiple myeloma cells, IL-6 and APRIL also supported MOPC315. BM cell growth in vitro, IL-5 had no effect. Depletion of eosinophils in vivo by IL-5 blockade led to a reduction of the early myeloma load. Consistent with this, myeloma growth in early stages was retarded in eosinophil-deficient Delta dblGATA-1 mice. Late myeloma stages were unaffected, possibly due to megakaryocytes compensating for the loss of eosinophils, since megakaryocytes were found to be in contact with myeloma cells in vivo and supported myeloma growth in vitro. We conclude that eosinophils and megakaryocytes in the niches for benign bone marrow plasma cells support the growth of malignant plasma cells. Further investigations are required to test whether perturbation of these niches represents a potential strategy for the treatment of multiple myeloma.},
  language  = {en}
}
@article{ShiKuaiLeietal.2016,
  author    = {Shi, Yaoyao and Kuai, Yue and Lei, Lizhen and Weng, Yuanyuan and Berberich-Siebelt, Friederike and Zhang, Xinxia and Wang, Jinjie and Zhou, Yuan and Jiang, Xin and Ren, Guoping and Pan, Hongyang and Mao, Zhengrong and Zhou, Ren},
  title     = {The feedback loop of LITAF and BCL6 is involved in regulating apoptosis in B cell non-Hodgkin's-lymphoma},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {47},
  doi       = {10.18632/oncotarget.12680},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166500},
  pages     = {77444-77456},
  year      = {2016},
  abstract  = {Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5\% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6. Therefore, we sought to explore the feedback loop between LITAF and BCL6 in B-NHL. Here, our data for the first time show that LITAF can repress expression of BCL6 by binding to Region A (-87 to +65) containing a putative LITAF-binding motif (CTCCC) within the BCL6 promoter. Furthermore, the regulation of BCL6 targets (PRDM1 or c-Myc) by LITAF may be associated with B-cell differentiation. Results also demonstrate that ectopic expression of LITAF induces cell apoptosis, activated by releasing cytochrome c, cleaving PARP and caspase 3 in B-NHL cells whereas knockdown of LITAF robustly protected cells from apoptosis. Interestingly, BCL6, in turn, could reverse cell apoptosis mediated by LITAF. Collectively, our findings provide a novel apoptotic regulatory pathway in which LITAF, as a transcription factor, inhibits the expression of BCL6, which leads to activation of the intrinsic mitochondrial pathway and tumor apoptosis. Our study is expected to provide a possible biomarker as well as a target for clinical therapies to promote tumor cell apoptosis.},
  language  = {en}
}
@phdthesis{Gross2003,
  author    = {Gross, Tim Philipp},
  title     = {Transkriptionelle Regulation des CD23a-Promotors in Zellen chronischer lymphatischer Leuk{\"a}mien vom B-Zelltyp},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-7344},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {Die Expression und Regulation des Gens f{\"u}r den niedrig affinen Immunglobulin E-Rezeptor, von welchem beim Menschen zwei Isoformen existieren, unterscheidet sich deutlich zwischen B-Lymphozyten der chronisch lymphatischen Leuk{\"a}mie und normalen B-Zellen. Eine Untersuchung auf Promotorebene erscheint daher interessant; da der Promotor der Isoform b schon relativ gut charakterisiert ist, wurde in dieser Arbeit der CD23a-Core-Promotor n{\"a}her betrachtet. Ein besonderes Augenmerk galt dabei putativen Bindungsstellen f{\"u}r STAT6. Das Bindungsverhalten von Transkriptionsfaktoren an Promotor-DNA wurde mit Gel-Retardierungsexperimenten (EMSA) untersucht. Hierzu wurden CD23a-Core-Promotor-Oligonukleotide zusammen mit Kernproteinextrakten aus Stimulationsans{\"a}tzen von B-CLL- und normalen B-Zellen mit IL-4, IFN-g und PMA genutzt. Die EMSA-Experimente zeigten trotz unterschiedlicher Stimulationsans{\"a}tze ein sich wiederholendes Bandenmuster, sodass die DNA-Protein-Interaktion auf Core-Promotorebene keine ausreichende Erkl{\"a}rung f{\"u}r die differentielle Regulation der Genexpression lieferte. Allerdings zeigten analoge EMSA-Versuche mit Kernextrakten einer EBV-transformierten Zelllinie ein leicht ver{\"a}ndertes Bandenmuster, was auf ein ver{\"a}ndertes Profil an Transkriptionsfaktoren am CD23a-Core-Promotor nach EBV-Transformation hindeuten kann. Eine weitere Analyse der Core-Promotorregion mittels der DNase-I-Footprint-Technik wurde durch die Klonierung geeigneter Vektoren und Etablierung einer Positivkontrolle vorbereitet. Da IL-4 den Hauptregulator auch der CD23a-Expression darstellt, war ein zentraler Teil der Arbeit die Charakterisierung von STAT6-Bindungsstellen im CD23a-Core-Promotor. Durch Sequenzanalyse wurden 2 putative STAT6-Bindungsstellen identifiziert. Mit Hilfe von Kompetitionsexperimenten konnte f{\"u}r eine der beiden Stellen (Nukleotidsequenz TAC CTGA GAA, Position 77-86 im CD23a-Core-Promotor) eine STAT6-Bindungsf{\"a}higkeit nachgewiesen werden; diese Bindungsstelle zeigte im Vergleich zu ihrem schon bekannten Gegenpart im CD23b-Promotor ein etwas schw{\"a}cheres Bindungsverm{\"o}gen f{\"u}r STAT6.Entscheidend f{\"u}r die Regulation der CD23-Expression sind wahrscheinlich das Zusammenspiel von STAT6 mit anderen Transkriptionsfaktoren wie Krox20 und NF-kB sowie alternative Signaltransduktionswege; auch Proto-Onkogene wie bcl-6 und Notch2 sind bei der Expression von CD23 von Bedeutung. Deren Rolle f{\"u}r die Pathogenese der B-CLL muss noch untersucht werden.},
  language  = {de}
}
@phdthesis{Duttu2005,
  author    = {Duttu, Vallabhapurapu Subrahmanya},
  title     = {Regulation of B lymphocyte terminal differentiation and death by the transcription factor Blimp-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-17158},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {B lymphocyte induced maturation protein-1 (Blimp-1) und X-box-binding protein-1" (XBP-1) sind als Transkriptionsfaktoren unverzichtbar f{\"u}r die terminale Differenzierung von B-Lymphozyten zu Immunglobulin (Ig)-sezernierenden Plasmazellen. Ebenso stellen die unfolded protein response (UPR) und das Spleißen von XBP-1, beides ausgel{\"o}st durch erh{\"o}hte Ig-Produktion, entscheidende Schritte auf dem Weg zur Plasmazellentstehung dar. Allerdings ist das Molek{\"u}l/ sind die Molek{\"u}le nach wie vor unbekannt, die diesen beiden Ereignissen in der Signalkaskade vorgeschaltet sind. Da die ektope Expression von Blimp-1 in B-Zellen hinreicht, diese zu Plasmazellen zu differenzieren, erscheint es plausibel, dass Blimp-1 das Molek{\"u}l sein k{\"o}nnte, das die Ausl{\"o}sung einer UPR und das Spleißen von XBP-1 steuert. Dieser M{\"o}glichkeit wurde durch ektope Expression von Blimp-1 in der Maus-B-Zell-Lymphomlinie WEHI 231 und in prim{\"a}ren B-Zellen aus der Milz von M{\"a}usen nachgegangen. Die ektope Expression von Blimp-1 f{\"u}hrte in beiden Zelltypen zur Erh{\"o}hung der Ig Produktion, zum Spleißen von XBP-1 und zur Sekretion von Immunglobulinen. Interessanterweise war der N-terminale Anteil von Blimp-1, bestehend aus den Aminos{\"a}uren 1-751, hinreichend, um diese Effekte auszul{\"o}sen, w{\"a}hrend der C-Terminus, der die Aminos{\"a}uren 465-856 umfaßte, keinen Effekt hatte. Dar{\"u}berhinaus, wurde die Expression von BIP, dessen Gen ein UPR-Zielgen ist, durch ektope Expression von Blimp-1 bzw. dessen N-Terminus in prim{\"a}ren B-Zellen erh{\"o}ht. Diese Ergebnisse zeigen deutlich, dass Blimp-1, speziell dessen N-terminale Dom{\"a}ne, hinreichend ist, um eine UPR und die Prozessierung von XBP-1 auszul{\"o}sen, was zur Ig-Sekretion von B-Zellen f{\"u}hrt.},
  subject      = {B-Lymphozyt},
  language  = {en}
}
@article{BehrPeitschHametneretal.2014,
  author    = {Behr, Daniel S. and Peitsch, Wiebke K. and Hametner, Christian and Lasitschka, Felix and Houben, Roland and Sch{\"o}nhaar, Kathrin and Michel, Julia and Dollt, Claudia and Goebeler, Matthias and Marx, Alexander and Goerdt, Sergij and Schmieder, Astrid},
  title     = {Prognostic value of immune cell infiltration, tertiary lymphoid structures and PD-L1 expression in Merkel cell carcinomas},
  series = {International Journal of Clinical and Experimental Pathology},
  volume    = {7},
  journal   = {International Journal of Clinical and Experimental Pathology},
  number    = {11},
  issn      = {1936-2625},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117720},
  pages     = {7610-7621},
  year      = {2014},
  abstract  = {Merkel cell carcinoma (MCC) is an aggressive, virus-associated, neuroendocrine tumor of the skin mainly affecting immunocompromised patients. Higher intratumoral infiltration with CD3 and CD8 positive T-cells is associated with a better prognosis, highlighting the relevance of the immune system for MCC development and progression. In this study 21 primary MCCs were stained with immune cell markers including CD3, CD4, CD8, CD68, CD20, and S100. Furthermore, tumor-infiltrating neutrophils, tertiary lymphoid structures and PD-L1 expression were analyzed and correlated with overall and recurrence free survival. All MCCs were Merkel Cell Polyomavirus positive. Overall and recurrence-free survival did not correlate with intra-and peritumoral CD3 and CD8 T-cell infiltration. In addition, no significant association regarding prognosis was found for tumor-associated neutrophils, tumor-associated macrophages or PD-L1 positivity in MCCs. Interestingly, the presence of tertiary lymphoid structures (TLS) in the tumor microenvironment significantly correlated with recurrence-free survival (P=0.025). In addition, TLS were significantly associated with a higher CD8/CD4 ratio in the tumor periphery (P=0.032), but not in the center of the tumor (P > 0.999). These results demonstrate for the first time that TLS, easily assessed in paraffin-embedded tissue in the tumor periphery of MCCs, may be a valuable prognostic factor indicating prolonged recurrence free survival.},
  language  = {en}
}