@article{BergesKerkauWerneretal.2016, author = {Berges, Carsten and Kerkau, Thomas and Werner, Sandra and Wolf, Nelli and Winter, Nadine and H{\"u}nig, Thomas and Einsele, Hermann and Topp, Max S. and Beyersdorf, Niklas}, title = {Hsp90 inhibition ameliorates CD4\(^{+}\) T cell-mediated acute Graft versus Host disease in mice}, series = {Immunity, Inflammation and Disease}, volume = {4}, journal = {Immunity, Inflammation and Disease}, number = {4}, doi = {10.1002/iid3.127}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168318}, pages = {463-473}, year = {2016}, abstract = {Introduction: For many patients with leukemia only allogeneic bone marrow transplantion provides a chance of cure. Co-transplanted mature donor T cells mediate the desired Graft versus Tumor (GvT) effect required to destroy residual leukemic cells. The donor T cells very often, however, also attack healthy tissue of the patient inducing acute Graft versus Host Disease (aGvHD)—a potentially life-threatening complication. Methods: Therefore, we used the well established C57BL/6 into BALB/c mouse aGvHD model to evaluate whether pharmacological inhibition of heat shock protein 90 (Hsp90) would protect the mice from aGvHD. Results: Treatment of the BALB/c recipient mice from day 0 to +2 after allogeneic CD4\(^{+}\) T cell transplantation with the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG) partially protected the mice from aGvHD. DMAG treatment was, however, insufficient to prolong overall survival of leukemia-bearing mice after transplantation of allogeneic CD4\(^{+}\) and CD8\(^{+}\) T cells. Ex vivo analyses and in vitro experiments revealed that DMAG primarily inhibits conventional CD4\(^{+}\) T cells with a relative resistance of CD4\(^{+}\) regulatory and CD8\(^{+}\) T cells toward Hsp90 inhibition. Conclusions: Our data, thus, suggest that Hsp90 inhibition might constitute a novel approach to reduce aGvHD in patients without abrogating the desired GvT effect.}, language = {en} } @article{FrankeVilnedaCostaetal.2015, author = {Franke, Katharina and Vilne, Baiba and da Costa, Olivia Prazeres and Rudelius, Martina and Peschel, Christian and Oostendorp, Robert A. J. and Keller, Ulrich}, title = {In vivo hematopoietic Myc activation directs a transcriptional signature in endothelial cells within the bone marrow microenvironment}, series = {Oncotarget}, volume = {6}, journal = {Oncotarget}, number = {26}, doi = {10.18632/oncotarget.5217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145844}, pages = {21827 -- 21839}, year = {2015}, abstract = {Cancer pathogenesis involves tumor-intrinsic genomic aberrations and tumor-cell extrinsic mechanisms such as failure of immunosurveillance and structural and functional changes in the microenvironment. Using Myc as a model oncogene we established a conditional mouse bone marrow transduction/transplantation model where the conditional activation of the oncoprotein Myc expressed in the hematopoietic system could be assessed for influencing the host microenvironment. Constitutive ectopic expression of Myc resulted in rapid onset of a lethal myeloproliferative disorder with a median survival of 21 days. In contrast, brief 4-day Myc activation by means of the estrogen receptor (ER) agonist tamoxifen did not result in gross changes in the percentage/frequency of hematopoietic lineages or hematopoietic stem/progenitor cell (HSPC) subsets, nor did Myc activation significantly change the composition of the non-hematopoietic microenvironment defined by phenotyping for CD31, ALCAM, and Sca-1 expression. Transcriptome analysis of endothelial CD45-Ter119-cells from tamoxifen-treated MycER bone marrow graft recipients revealed a gene expression signature characterized by specific changes in the Rho subfamily pathway members, in the transcription-translation-machinery and in angiogenesis. In conclusion, intra-hematopoietic Myc activation results in significant transcriptome alterations that can be attributed to oncogene-induced signals from hematopoietic cells towards the microenvironment, e. g. endothelial cells, supporting the idea that even pre-leukemic HSPC highjack components of the niche which then could protect and support the cancer-initiating population.}, language = {en} } @article{HirschMartinoWardetal.2013, author = {Hirsch, Hans H. and Martino, Rodrigo and Ward, Katherine N. and Boeckh, Michael and Einsele, Hermann and Ljungman, Per}, title = {Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for Diagnosis and Treatment of Human Respiratory Syncytial Virus, Parainfluenza Virus, Metapneumovirus, Rhinovirus, and Coronavirus}, series = {Clinical Infectious Diseases}, volume = {56}, journal = {Clinical Infectious Diseases}, number = {2}, doi = {10.1093/cid/cis844}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124758}, pages = {258-266}, year = {2013}, abstract = {Community-acquired respiratory virus (CARV) infections have been recognized as a significant cause of morbidity and mortality in patients with leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). Progression to lower respiratory tract infection with clinical and radiological signs of pneumonia and respiratory failure appears to depend on the intrinsic virulence of the specific CARV as well as factors specific to the patient, the underlying disease, and its treatment. To better define the current state of knowledge of CARVs in leukemia and HSCT patients, and to improve CARV diagnosis and management, a working group of the Fourth European Conference on Infections in Leukaemia (ECIL-4) 2011 reviewed the literature on CARVs, graded the available quality of evidence, and made recommendations according to the Infectious Diseases Society of America grading system. Owing to differences in screening, clinical presentation, and therapy for influenza and adenovirus, ECIL-4 recommendations are summarized for CARVs other than influenza and adenovirus.}, language = {en} } @article{KredelKunzmannSchlegeletal.2017, author = {Kredel, Markus and Kunzmann, Steffen and Schlegel, Paul-Gerhardt and W{\"o}lfl, Matthias and Nordbeck, Peter and B{\"u}hler, Christoph and Lotz, Christopher and Lepper, Philipp M. and Wirbelauer, Johannes and Roewer, Norbert and Muellenbach, Ralf M.}, title = {Double Peripheral Venous and Arterial Cannulation for Extracorporeal Membrane Oxygenation in Combined Septic and Cardiogenic Shock}, series = {American Journal of Case Reports}, volume = {18}, journal = {American Journal of Case Reports}, doi = {10.12659/AJCR.902485}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158193}, pages = {723-727}, year = {2017}, abstract = {Background: The use of venoarterial extracorporeal membrane oxygenation (va-ECMO) via peripheral cannulation for septic shock is limited by blood flow and increased afterload for the left ventricle. Case Report: A 15-year-old girl with acute myelogenous leukemia, suffering from severe septic and cardiogenic shock, was treated by venoarterial extracorporeal membrane oxygenation (va-ECMO). Sufficient extracorporeal blood flow matching the required oxygen demand could only be achieved by peripheral cannulation of both femoral arteries. Venous drainage was performed with a bicaval cannula inserted via the left V. femoralis. To accomplish left ventricular unloading, an additional drainage cannula was placed in the left atrium via percutaneous atrioseptostomy (va-va-ECMO). Cardiac function recovered and the girl was weaned from the ECMO on day 6. Successful allogenic stem cell transplantation took place 2 months later. Conclusions: In patients with vasoplegic septic shock and impaired cardiac contractility, double peripheral venoarterial extracorporeal membrane oxygenation (va-va-ECMO) with transseptal left atrial venting can by a lifesaving option.}, language = {en} } @article{ManukjanRippergerVenturinietal.2016, author = {Manukjan, Georgi and Ripperger, Tim and Venturini, Letizia and Stadler, Michael and G{\"o}hring, Gudrun and Schambach, Axel and Schlegelberger, Brigitte and Steinemann, Doris}, title = {GABP is necessary for stem/progenitor cell maintenance and myeloid differentiation in human hematopoiesis and chronic myeloid leukemia}, series = {Stem Cell Research}, volume = {16}, journal = {Stem Cell Research}, number = {3}, doi = {10.1016/j.scr.2016.04.007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168165}, pages = {677-681}, year = {2016}, abstract = {Maintenance of hematopoietic stem cells and their potential to give rise to progenitors of differentiated lymphoid and myeloid cells are accomplished by a network of regulatory processes. As a part of this network, the heteromeric transcription factor GA-binding protein (GABP) plays a crucial role in self-renewal of murine hematopoietic and leukemic stem cells. Here, we report the consequences of functional impairment of GABP in human hematopoietic and in leukemic stem/progenitor cells. Ectopic overexpression of a dominant-negative acting GABP mutant led to impaired myeloid differentiation of CD34\(^{+}\) hematopoietic stem/progenitor cells obtained from healthy donors. Moreover, drastically reduced clonogenic capacity of leukemic stem/progenitor cells isolated from bone marrow aspirates of chronic myeloid leukemia (CML) patients underlines the importance of GABP on stem/progenitor cell maintenance and confirms the relevance of GABP for human myelopoiesis in healthy and diseased states.}, language = {en} } @article{WiegeringAndresSchlegeletal.2013, author = {Wiegering, Verena and Andres, Oliver and Schlegel, Paul G. and Deinlein, Frank and Eyrich, Matthias and Sturm, Alexander}, title = {Hyperfibrinolysis and acquired factor XIII deficiency in newly diagnosed pediatric malignancies}, series = {Haematologica}, volume = {98}, journal = {Haematologica}, number = {8}, doi = {10.3324/haematol.2013.089045}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130569}, pages = {E90-E91}, year = {2013}, abstract = {No abstract available}, language = {en} }