@article{VaragnoloLinObieretal.2015,
  author    = {Varagnolo, Linda and Lin, Quiong and Obier, Nadine and Plass, Christoph and Dietl, Johannes and Zenke, Martin and Claus, Rainer and M{\"u}ller, Albrecht M.},
  title     = {PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem and progenitor cells},
  series = {Scientific Reports},
  volume    = {5},
  journal   = {Scientific Reports},
  number    = {12319},
  doi       = {10.1038/srep12319},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148374},
  year      = {2015},
  abstract  = {Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential we profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells were cultured in serum-free medium together with SCF, TPO, FGF, with or without Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells. Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending on the cytokine cocktail, cells show different HK4me3 and H3K27me3 levels. Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3 levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture-associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our data reveal chromatin dynamics that underlie the culture-associated loss of engraftment potential. We identify PRC2 component EZH2 as being involved in the loss of engraftment potential during the in vitro expansion of HPSCs.},
  language  = {en}
}
@article{LuekeHallerUtpateletal.2022,
  author    = {L{\"u}ke, Florian and Haller, Florian and Utpatel, Kirsten and Krebs, Markus and Meidenbauer, Norbert and Scheiter, Alexander and Spoerl, Silvia and Heudobler, Daniel and Sparrer, Daniela and Kaiser, Ulrich and Keil, Felix and Schubart, Christoph and T{\"o}gel, Lars and Einhell, Sabine and Dietmaier, Wolfgang and Huss, Ralf and Dintner, Sebastian and Sommer, Sebastian and Jordan, Frank and Goebeler, Maria-Elisabeth and Metz, Michaela and Haake, Diana and Scheytt, Mithun and Gerhard-Hartmann, Elena and Maurus, Katja and Br{\"a}ndlein, Stephanie and Rosenwald, Andreas and Hartmann, Arndt and M{\"a}rkl, Bruno and Einsele, Hermann and Mackensen, Andreas and Herr, Wolfgang and Kunzmann, Volker and Bargou, Ralf and Beckmann, Matthias W. and Pukrop, Tobias and Trepel, Martin and Evert, Matthias and Claus, Rainer and Kerscher, Alexander},
  title     = {Identification of disparities in personalized cancer care — a joint approach of the German WERA consortium},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {20},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14205040},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290311},
  year      = {2022},
  abstract  = {(1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in W{\"u}rzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy.},
  language  = {en}
}
@article{LiebersDuellFitzgeraldetal.2021,
  author    = {Liebers, Nora and Duell, Johannes and Fitzgerald, Donnacha and Kerkhoff, Andrea and Noerenberg, Daniel and Kaebisch, Eva and Acker, Fabian and Fuhrmann, Stephan and Leng, Corinna and Welslau, Manfred and Chemnitz, Jens and Middeke, Jan-Moritz and Weber, Thomas and Holtick, Udo and Trappe, Ralf and Pfannes, Roald and Liersch, Ruediger and Spoer, Christian and Fuxius, Stefan and Gebauer, Niklas and Caill{\´e}, L{\´e}andra and Geer, Thomas and Koenecke, Christian and Keller, Ulrich and Claus, Rainer and Mougiakakos, Dimitrios and Mayer, Stephanie and Huettmann, Andreas and Pott, Christiane and Trummer, Arne and Wulf, Gerald and Brunnberg, Uta and Bullinger, Lars and Hess, Georg and Mueller-Tidow, Carsten and Glass, Bertram and Lenz, Georg and Dreger, Peter and Dietrich, Sascha},
  title     = {Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas},
  series = {Blood Advances},
  volume    = {5},
  journal   = {Blood Advances},
  doi       = {10.1182/bloodadvances.2020004155},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369173},
  pages     = {2707-2716},
  year      = {2021},
  abstract  = {The antibody-drug conjugate polatuzumab vedotin (pola) has recently been approved in combination with bendamustine and rituximab (pola-BR) for patients with refractory or relapsed (r/r) large B-cell lymphoma (LBCL). To investigate the efficacy of pola-BR in a real-world setting, we retrospectively analyzed 105 patients with LBCL who were treated in 26 German centers under the national compassionate use program. Fifty-four patients received pola as a salvage treatment and 51 patients were treated with pola with the intention to bridge to chimeric antigen receptor (CAR) T-cell therapy (n = 41) or allogeneic hematopoietic cell transplantation (n = 10). Notably, patients in the salvage and bridging cohort had received a median of 3 prior treatment lines. In the salvage cohort, the best overall response rate was 48.1\%. The 6-month progression-free survival and overall survival (OS) was 27.7\% and 49.6\%, respectively. In the bridging cohort, 51.2\% of patients could be successfully bridged with pola to the intended CAR T-cell therapy. The combination of pola bridging and successful CAR T-cell therapy resulted in a 6-month OS of 77.9\% calculated from pola initiation. Pola vedotin-rituximab without a chemotherapy backbone demonstrated encouraging overall response rates up to 40\%, highlighting both an appropriate alternative for patients unsuitable for chemotherapy and a new treatment option for bridging before leukapheresis in patients intended for CAR T-cell therapy. Furthermore, 7 of 12 patients with previous failure of CAR T-cell therapy responded to a pola-containing regimen. These findings suggest that pola may serve as effective salvage and bridging treatment of r/r LBCL patients.},
  language  = {en}
}