Outstanding science with an interdisciplinary emphasis is the hallmark of research in the Clinic for Internal Medicine II of the Jena University Hospital. This is reflected in our researchers’ participation in several joint research projects as well as in the support they receive from the German Research Council (DFG), the Federal Ministry of Education and Research (BMBF) and further foundations.
The research activities in the Department of Hematology and Medical Oncology focus on basic research into the molecular mechanisms of signal transduction in solid tumors and hematological malignancies.
In the field of translational research our scientists investigate the active principles of new substance classes for the treatment of leukemias and lymphomas as well as the diagnostic relevance of circulating tumor cells. Application of innovative therapies in multicenter trials is the focus of clinical research.
Click below for a description of each research group.
Joachim Clement, Dr. rer. biol. hum. (Group Leader)
Abteilung Hämatologie und Internistische Onkologie
Klinik Innere Medizin II
Universitätsklinikum Jena
Phone.: +49 (3641) 9-325820
Fax: +49 (3641) 9-325822
email:
Lena Belfi, B.Sc., Masterstudent
Cornelia Jörke, MTA
Frauke Seeber, Doktorandin
Malika Sutter, B.Sc., Masterstudentin
Martin Taeger, Doktorand
Ekaterina Zheveliuk, M.Sc., Doktorandin, LG Stipendiatin
The entire nature of tumor cells and their communication with the microenvironment is complex. We are interested in the mechanism, which drive the dissemination of tumor cells from the primary tumor and allow the survival of these cells in the circulation and finally their evasion. An import role in these processes plays the bone morphogenetic protein signaling network. In collaboration with partners from academia and industry we develop new procedures to identify and isolate the entirety of circulating tumor cells from the peripheral blood. Novel photonic technologies and innovative nanomaterials contribute to a significant part to this approach.
Magnetic metallic nanoparticles are widely used tools to isolate and label cells, e.g. circulating tumor cells. We are interested in understanding the cellular processes during the interaction of nanomaterials with human cells. In focus are overall cell vitality, intracellular transport mechanisms and inflammatory response. The life cycle of nanomaterials is studied in long-term cell culture models.
The detection and identification of circulating tumor cells is challenging. The proportion of these cells is very low in the peripheral blood of tumor patients. The cell population is highly variable which requires an in-depth investigation on a single cell level. A further characterization on the molecular level is needed for future advances in cancer diagnosis and therapy.
Bone morphogenetic proteins are a subgroup of the Transforming Growth Factor beta superfamily. They are important regulators of embryogenesis, organogenesis and tumorigenesis. We could show that BMP-2 keeps cells in a “susceptible state” that can take various directions depending on further signals.
Rosenfeldt, S., Mickoleit, F., Jörke, C., Clement, J.H., Markert, S., Jérôme, V., Schwarzinger, S., Freitag, R., Schüler, D., Uebe, R., Schenk, A.S. 2020. Towards standardized purification and regeneration of bacterial magnetic nanoparticles for future in vivo applications. Acta Biomaterialia: https://doi.org/10.1016/j.actbio.2020.07.042
Dutz, S., Buske, N., Landers, J., Gräfe, C., Wende, H., Clement, J.H. 2020. Biocompatible magnetic fluids of Co-doped iron oxide nanoparticles with tunable magnetic properties. Nanomaterials: 10: 1019; doi.org/10.3390/nano10061019
Mihajlović, J., Diehl, L.M.A., Hochhaus, A., Clement J.H. 2019. Inhibition of bone morphogenetic protein signaling reduces viability, growth and migratory potential of non-small cell lung carcinoma cells. J. Cancer Res. Clin. Oncol. 145: 2675-2687.
Alcala, N., Leblay, N., Gabriel, A., Mangiante, L., Hervas Marin, D., Giffon, T., Sertier, A.S., Ferrari, a., Derks, J., Ghantous, A., Delhomme, T.M., Chabrier, A., Cuenin, C., Abedi-Ardekani, B., Boland, A., Caux, C., Altmueller, A., Durand, G., Voegele, C., Boyault, S., Lemaitre, N., Lorimier, P., Toffart, A.C., Mc Leer, A., Solterman, A., Clement, J.H., Saenger, J., Field, J.K., Brevet, M., Blanc-Fournier, C., Galateau-Salle, F., Le Stang, N., Damiola, F., Russell, P., Wright, G., Roz, L., Lacomme, S., Vignaug, J.M., Hofman, V., Hofman, P., Brustugun, O.T., Lund-Iversen, M., Thomas de Montpreville, V., Muscarella, L.A., Graziano, P., Volante, M., Papotti, M.G., Brcic, L., Popper, H., Deleuze, J.F., Herceg, Z., Viari, A., Nuernberg, P., McKay, J.D., Sandoval, J., Hernandez-Vargas, H., Brambilla, E., Speel, E.J., Girard, N., Lantuejoul, S., Foll, M., Fernandez-Cuesta, L. 2019. Integrative and comparative analyses of multi-omics data identify clinically relevant molecular groups of pulmonary carcinoids and unveil the existence of supra-atypical carcinoids. Nature Commun. 10: 3407; doi.org/10.1038/s41467-019-11276-9
Gräfe, C., von der Lühe, M., Weidner, A., Globig, P., Clement, J.H., Dutz, S., Schacher, F.H. 2019. Protein Corona Formation and its Constitutional Changes on Magnetic Nanoparticles in Serum featuring a Polydehydroalanine Coating: Effects of Charge and Incubation Conditions. Nanotechnology 30(26):265707. doi: 10.1088/1361-6528/ab0ed0
Müller, E.K., Gräfe, C., Wiekhorst, F., Bergemann, C., Weidner, A., Dutz, S., Clement, J.H. 2018. Magnetic nanoparticles interact and pass an in vitro co-culture blood-placenta model. Nanomaterials 8: 108; doi:10.3390/nano8020108
George, J., Walter, V., Peifer, M., Alexandrov, L.B., Seidel, D., Leenders, F., Maas, L., Müller, C., Dahmen, I., Delhomme, T.M., Ardin, M., Leblay, N., Byrnes, G., Sun, R., De Reynies, A., McLeer-Florin, A., Bosco, G., Malchers, F., Menon, R., Altmüller, J., Becker, C., Nürnberg, P., Achter, V., Lang, U., Schneider, P.M., Bogus, M., Soloway, M.G., Wilkerson, M.D., Cun, Y., McKay, J.D., Moro-Sibilot, D., Brambilla, C.G., Lantuejoul, S., Lemaitre, N., Soltermann, A., Weder, W., Tischler, V., Brustugun, O.T., Lund-Iversen, M., Helland, Å., Solberg, S., Ansén, S., Wright, G., Solomon, B., Roz, L., Pastorino, U., Petersen, I., Clement, J.H., Sänger, J., Wolf, J., Vingron, M., Zander, T., Perner, S., Travis, W.D., Haas, S.A., Olivier, M., Foll, M., Büttner, R., Hayes, D.N., Brambilla, E., Fernandez-Cuesta, L., Thomas, R.K. 2018. Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nat Commun. 9: 1048.
Complete list of publications here.
We encourage applications for Bachelor’s and Master’s theses as well as doctoral theses in the fields of medicine (experimental) and the life sciences. For more information, please contact Dr. Joachim Clement ().
Deutsche Forschungsgemeinschaft
BMBF
Dr. Rainald Stromeyer-Stiftung
Jenny Rinke, MSc
Dr. rer. nat. Vivien Schäfer
Dr. med. Nils Winkelmann
Dr. med. Alexander Kaiser
Dr. med. Jochen Frietsch
Dr. med. Jakob Hammersen
Susanne Möbius, MSc
Anna Hinze, MSc
Lioba Ruppert (cand. med.)
Julia Hagen (cand. med.)
Marie-Therese Ott (cand. med.)
Kristian Kamp (cand. med.)
Danica Midic (Masterarbeit)
Anja Waldau (MTA)
The group is working on the molecular pathogenesis, diagnosis and therapy of myeloid leukemia with a focus on chronic myelogenous leukemia (CML) and related myeloproliferative (MPN) and myelodysplastic (MDS) diseases. In close connection between the clinic and the laboratory, several translational research projects in the fields of molecular genetics, epigenetics, clonal evolution and aging are being worked on. Using state-of-the-art sequencing techniques (pyrosequencing, next-generation sequencing) and array technology, genome-wide studies of genetic and epigenetic alterations are performed and functionally characterized in the cell model. The data obtained are analyzed and correlated with clinical parameters (e.g., response to therapy and disease progression). As a result, new prognostic markers and molecular targets can be identified, which could help to develop new targeted therapies for affected patients.
Bei Interesse an einer experimentellen Doktorarbeit bitte PD Dr. Ernst kontaktieren.
Bundesministerium für Bildung und Forschung (BMBF), Deutsche José-Carreras-Leukämie-Stiftung, Hector-Stiftung
Dr. Tino Schenk
Klinik für Innere Medizin II
Universitätsklinikum Jena
Abteilung Hämatologie und Internistische Onkologie
Labor im
Institut für Molekulare Zellbiologie
Zentrum für Molekulare Biomedizin (CMB)
Hans-Knöll-Strasse 2
07745 Jena
Jacqueline Schütt (Masterstudentin)
Sergei Silaev (Masterstudent)
Franziska Fiedler (Doktorandin, Medizin)
Clara Stanko (PhD-Studentin)
Unsere Arbeitsgruppe beschäftigt sich mit der Erforschung genetischer und epigenetischer Faktoren, welche dem Differenzierungsblock leukämischer Stammzellen und Blasten zugrunde liegen. Der Schwerpunkt richtet sich hierbei auf der Freisetzung des kurativen Potenzials der All-trans-Retinsäure (ATRA) in der Akuten Myeloischen Leukämie (AML). In aktuellen Forschungsvorhaben sollen die Mechanismen der pro-differenzierenden Wirkung von Inhibitoren der Histon H3 Lysin 4 Demethylase LSD1 in Kombination mit ATRA entschlüsselt und neue epigenetische Ziele identifiziert werden, welche die ATRA vermittelte Aufhebung des Differenzierungsblocks der AML ermöglichen.
M. Kahl, A. Brioli, M. Bens, F. Perner, A. Kresinsky, U. Schnetzke, A. Hinze, Y. Sbirkov, S. Stengel, G. Simonetti, G. Martinelli, K. Petrie, A. Zelent, F. Boehmer, M. Groth, T. Ernst, F. Heidel, S. Scholl, A. "Hochhaus, and T. Schenk, “The acetyltransferase GCN5 maintains ATRA-resistance in non-APL AML”, Leukemia, Epub ahead of print, https://doi.org/10.1038/s41375-019-0581-y.
A. Steube, T. Schenk, A. Tretyakov, and H. P. Saluz, “High-intensity UV laser ChIP-seq for the study of protein-DNA interactions in living cells”, Nature Communications, vol. 8, article 1303, Nov. 2017.
S. Göllner, T. Oellerich, S. Agrawal-Singh, T. Schenk, H.-U. U. Klein, C. Rohde, C. Pabst, T. Sauer, M. Lerdrup, S. Tavor, F. Stölzel, S. Herold, G. Ehninger, G. Köhler, K.-T. T. Pan, H. Urlaub, H. Serve, M. Dugas, K. Spiekermann, B. Vick, I. Jeremias, W. E. Berdel, K. Hansen, A. Zelent, C. Wickenhauser, L. P. Müller, C. Thiede, and C. Müller-Tidow, “Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia”, Nature Medicine, vol.23, pp. 69-78, Jan 2017.
T. Schenk, S. Stengel, and A. Zelent, “Unlocking the potential of retinoic acid in anticancer therapy.”, British Journal of Cancer, 111(11):2039-45, Nov. 2014.
T. Schenk, W. C. Chen, S. Göllner, L. Howell, L. Jin, K. Hebestreit, H.-U. Klein, A. C. Popescu, A. Burnett, K. Mills, R. a Casero, L. Marton, P. Woster, M. D. Minden, M. Dugas, J. C. Y. Wang, J. E. Dick, C. Müller-Tidow, K. Petrie, and A. Zelent, “Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia.”, Nature Medicine, vol. 18, no. 4, pp. 605–11, Apr. 2012.
C. L. Alvares, T. Schenk, S. Hulkki, T. Min, G. Vijayaraghavan, J. Yeung, D. Gonzalez, C. W. E. So, M. Greaves, I. Titley, K. Bartolovic, and G. Morgan, “Tyrosine kinase inhibitor insensitivity of non-cycling CD34+ human acute myeloid leukaemia cells with FMS-like tyrosine kinase 3 mutations”, British Journal of Haematology, vol. 154, no. 4, pp. 457–65, Aug. 2011.
E. F. Farias, K. Petrie, B. Leibovitch, J. Murtagh, M. B. Chornet, T. Schenk, A. Zelent, and S. Waxman, “Interference with Sin3 function induces epigenetic reprogramming and differentiation in breast cancer cells.,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 26, pp. 11811–6, Jun. 2010.
T. Schenk, S. Stengel, S. Goellner, D. Steinbach, and H. P. Saluz, “Hypomethylation of PRAME is responsible for its aberrant overexpression in human malignancies,” Genes, Chromosomes & Cancer, vol. 804, no. April, pp. 796–804, 2007.
S. Goellner, D. Steinbach, T. Schenk, B. Gruhn, F. Zintl, E. Ramsay, and H. P. Saluz, “Childhood acute myelogenous leukaemia: association between PRAME, apoptosis- and MDR-related gene expression.,” European journal of cancer (Oxford, England : 1990), vol. 42, no. 16, pp. 2807–14, Nov. 2006.
Bei Interesse an einer experimentellen Bachelor- oder Masterarbeit schreiben sie bitte eine E-Mail an oder stellen sich persönlich im Labor vor.
Deutsche Forschungsgemeinschaft, IZKF, Deutsche Krebshilfe
Landesgraduiertenstipendium (Faezeh Zadegan)
Unsere Arbeitsgruppe beschäftigt sich mit verschiedenen Aspekten der akuten myeloischen Leukämie (AML).
1. Einfluss von “single nucleotide polymorphisms” (SNPs) des angeborenen Immunsystems auf Infektionen bei AML-Patienten
Wir analysieren systematisch SNPs des angeborenen Immunsystems und deren Einfluss auf infektiologische Komplikationen bei AML-Patienten. Wir konnten kürzlich zeigen, dass SNPs von TLR2 und TLR4 in signifikantem Zusammenhang mit dem Auftreten von Sepsis oder Pneumonie nach AML-Induktionschemotherapie stehen.
Derzeit untersuchen wir mehr als 30 funktionell bedeutende SNPs der angeborenen Immunität und deren Einfluss auf Infektkomplikationen bei ca. 200 AML-Patienten nach Induktionstherapie. Hier kommt der exakten klinischen Klassifikation von Pilzinfektionen (proven vs. probable vs. possible IFD) eine große Bedeutung zu.
2. Charakterisierung der Signaltransduktion von FLT3-ITD in Abhängigkeit von Lokalisation und Peptidsequenz (z.B. “Y-X-Y” –Motive) der Längenmutationen
Längenmutationen der Rezeptortyrosinkinase FLT3, sog. FLT3-ITD (internal tandem duplications) stellen die häufigste molekulargenetische Aberration bei AML-Patienten dar, welche mit einer schlechten Prognose assoziiert ist. Neben Lokalisation und Länge einer ITD variiert bspw. auch die Anzahl sog. „Y-X-Y-Motive“ innerhalb sowie im Randbereich der ITDs. Die patienten-spezifische Variabilität hinsichtlich derartiger „Y-X-Y-Motive“ stellt neben der ITD-Lokalisation (JM- vs. TKD) einen mutmaßlich wichtigen Faktor im Verständnis der differentiellen Signaltransduktion von FLT3-ITDs sowie daraus abgeleitet für klinisch relevante Resistenzmechanismen dar.
Unsere Arbeitsgruppe hat daher verschiedene Varianten von FLT3-ITDs generiert und aktuell durch retroviralen Gentransfer in 32D-Zellen zur stabilen Expression gebracht. Die mit diesen Zellmodellen geplanten Untersuchungen sollen insbesondere die differentielle Signaltransduktion als auch die von der ITD-Sequenz abhängige Sensitivität gegenüber klinisch relevanten FLT3-Inhibitoren (u.a. AC220, Sorafenib, Ponatinib) untersuchen.
2016
Winkelmann N, Desole M, Hilgendorf I, Ernst T, Sayer HG, Kunert C, Mügge LO, Hochhaus A, Scholl S. Comparison of two dose levels of cyclophosphamide for successful stem cell mobilization in myeloma patients. J Cancer Res Clin Oncol. 2016 Dec;142(12):2603-2610.
Fleischmann M, Schnetzke U, Schrenk KG, Schmidt V, Sayer HG, Hilgendorf I, Hochhaus A, Scholl S. Outcome of FLT3-ITD-positive acute myeloid leukemia: impact of allogeneic stem cell transplantation and tyrosine kinase inhibitor treatment. J Cancer Res Clin Oncol. 2016 Oct 24. [Epub ahead of print]
Göpel W, Schnetzke U, Hochhaus A, Scholl S. Functional acute liver failure after treatment with pegylated asparaginase in a patient with acute lymphoblastic leukemia: potential impact of plasmapheresis. Ann Hematol. 2016 Oct;95(11):1899-901.
Fischer M, Spies-Weisshart B, Schrenk K, Gruhn B, Wittig S, Glaser A, Hochhaus A, Scholl S, Schnetzke U. Polymorphisms of Dectin-1 and TLR2 Predispose to Invasive Fungal Disease in Patients with Acute Myeloid Leukemia. PLoS One. 2016 Mar 10;11(3):e0150632. doi: 10.1371/journal.pone.0150632.
Desole M, Schrenk KG, Schnetzke U, Hochhaus A, Scholl S. Detection of Enterococcus spp. in bronchoalveolar lavage fluid of patients with high-risk neutropenia: May it be ignored ? J Cancer Res Clin Oncol. 2016 May;142(5):1133-6.
2015
Schrenk KG, Katenkamp K, Felber J, Mügge LO, Hochhaus A, Scholl S. Lower gastrointestinal bleeding in a patient with Crohn's disease and plasma cell leukemia in remission. Ann Hematol. 2015 Dec;94(12):2063-5.
Schrenk KG, Schnetzke U, Stegemann K, von Lilienfeld-Toal M, Hochhaus A, Scholl S. Efficacy of antifungal prophylaxis with oral suspension posaconazole during induction chemotherapy of acute myeloid leukemia. J Cancer Res Clin Oncol. 2015 Sep;141(9):1661-8.
Schnetzke U, Spies-Weisshart B, Yomade O, Fischer M, Rachow T, Schrenk K, Glaser A, von Lilienfeld-Toal M, Hochhaus A, Scholl S. Polymorphisms of Toll-like receptors (TLR2 and TLR4) are associated with the risk of infectious complications in acute myeloid leukemia. Genes Immun. 2015 Jan-Feb;16(1):83-8.
2014
Schnetzke U, Spies-Weisshart B, Yomade O, Fischer M, Rachow T, Schrenk K, Glaser A, von Lilienfeld-Toal M, Hochhaus A, Scholl S. Polymorphisms of Toll-like receptors (TLR2 and TLR4) are associated with the risk of infectious complications in patients with acute myeloid leukemia. Genes Immun. 2014 Nov 27. doi: 10.1038/gene.2014.67. [Epub ahead of print]
Schnetzke U, Schrenk K, Spies-Weisshart B, Kunert C, Hochhaus A, Scholl S. Different clones of acute leukemia after successful treatment of Hodgkin's disease. Ann Hematol. 2014 May 7. [Epub ahead of print] No abstract available.
Schnetzke U, Fix P, Spies-Weisshart B, Schrenk K, Glaser A, Fricke HJ, La Rosée P, Hochhaus A, Scholl S. Efficacy and feasibility of cyclophosphamide combined with intermediate- dose or high-dose cytarabine for relapsed and refractory acute myeloid leukemia (AML). J Cancer Res Clin Oncol. 2014 Aug;140(8):1391-7.
2013
Schnetzke U, Fischer M, Spies-Weisshart B, Zirm E, Hochhaus A, Müller JP, Scholl S. The E3 ubiquitin ligase TRAF2 can contribute to TNF-α resistance in FLT3-ITD-positive AML cells. Leuk Res. 2013 Nov;37(11):1557-64.
Spies-Weisshart B, schilling K, Böhmer FD, Hochhaus A, Sayer HG, Scholl S (2013) Lack of association of platelet-derived growth factor (PDGF) receptor autoantibodies and severity of chronic graft-versus-host disease (GvHD) J Cancer Res Clin Oncol 139: 1397-1404
Yomade O, Spies-Weisshart B, Glaser A, Schnetzke U, Hochhaus A, Scholl S (2013) Impact of NOD2 polymorphisms on infectious complications following chemotherapy in patients with acute myeloid leukaemia. Annals of hematology 92: 1071-1077
2012
Schnetzke U, Fischer M, Kuhn AK, Spies-Weisshart B, Zirm E, Hochhaus A, Müller JP, Scholl S (2012) The E3 ubiquitin ligase TRAF6 inhibits LPS-induced AKT activation in FLT3-ITD-positive MV4-11 AML cells. Journal of cancer research and clinical oncology 139: 605-615
Zirm E, Spies-Weisshart B, Heidel F, Schnetzke U, Böhmer FD, Hochhaus A, Fischer T, Scholl S (2012) Ponatinib may overcome resistance of FLT3-ITD harbouring additional point mutations, notably the previously refractory F691I mutation. British journal of haematology 157: 483-492
2011
Rommeley M, Spies-Weisshart B, Schilling K, Hochhaus A, Sayer HG, Scholl S (2011) Reconstitution and functional analyses of neutrophils and distinct subsets of monocytes after allogeneic stem cell transplantation. Journal of cancer research and clinical oncology 137: 1293-1300
Scholl S, Spies-Weisshart B, Klink A, Muegge LO, Fricke HJ, Hochhaus A (2011) Secondary resistance to sorafenib in two patients with acute myeloid leukemia (AML) harboring FLT3-ITD mutations. Annals of hematology 90: 473-475
Bei Interesse an einer experimentellen medizinischen Promotion bitte Kontakt per E-Mail. Neben einem Laborpraktikum in den Semesterferien sehen wir eine kontinuierliche Präsenz für mindestens ein Semester als unabdingbar für die Realisierung einer medizinischen Doktorarbeit an.
“Förderprogramm Infektiologie”, Firma Gilead
Deutsche Krebshilfe
Deutsche José Carreras Leukämie-Stiftung
Während der Zellteilung durchlaufen alle Zellen bestimmte Phasen des Zellzyklus. Zu diesen Zeitpunkten erfolgen wichtige Schritte wie z.B. die Verdopplung der DNA in der S-Phase oder die Trennung der Schwesterchromatiden in der Mitose. Fehler während des Zellzyklus führen zum Arrest der Zellteilung oder zur Entstehung von Tumorzellen. Die Arbeitsgruppe untersucht die wichtigen Zellzyklusregulatoren Anaphase-Promoting Complex (APC) und Separase. Die Ubiquitinligase Anaphase-Promoting Complex/ Cyclosome (APC/C) ist durch Ubiquitinierung regulatorischer Proteine für den geordneten Ablauf des Zellzyklus von zentraler Bedeutung. Darüber hinaus hat der APC/C auch Funktionen in postmitotischen Zellen und verhindert den unkontrollierten Wiedereintritt von ruhenden Zellen in den Zellzyklus. Auch an Zellzyklus unabhängigen Regulationsmechanismen ist der APC/C beteiligt. Im Gegensatz zur bekannten Funktion im Zellzyklus sind die Zellzyklus unabhängigen Funktionen von APC/C weitgehend ungeklärt. Die Protease Separase spaltet in der Mitose den Cohesin Complex und ermöglicht damit die Trennung der Schwesterchromatiden. Das Verständnis grundlegender Mechanismen der Zellzyklusregulation kann auf Leukämiezellen übertragen werden und zu neuen Therapieoptionen führen.
Schrenk KG, Frosinski J, Scholl S, Otto S, La Rosée P, Hochhaus A and Pletz M. Successful treatment of neutropenic MRSA bacteremia with septic superior vena cava thrombus and cerebral embolism using high-dose daptomycin. 2015. Ann Hematol. Epub ahead of print.
Schrenk KG, Katenkamp K, Felber, J, Mügge LO, Hochhaus A. and Scholl S. Lower gastrointestinal bleeding in a patient with Crohn´s disease and plasma cell leukemia in remission. 2015. Ann Hematol 94(12): 2063-5.
Schrenk KG, Schnetzke U, Stegemann K, von Lilienfeld-Toal M, Hochhaus A and Scholl S. 2015. Efficacy of antifungal prophylaxis with oral suspension posaconazole during induction chemotherapy of acute myeloid leukemia. 2015. J.Cancer Res.Clin.Oncol 141(9):1661-8.
Schnetzke U, Spies-Weisshart B, Yomade O, Fischer M, Rachow T, Schrenk K, Glaser A, von Lilienfeld-Toal M, Hochhaus A and Scholl, S. 2014. Polymorphisms of Toll-like receptors (TLR2 and TLR4) are associated with the risk of infectious complications in patients with acute myeloid leukemia. Genes Immun 16(1): 83-88.
Schnetzke U, Fix P, Spies-Weisshart B, Schrenk K, Glaser A, Fricke H-J, La Roseé P, Hochhaus A and Scholl S. 2014. Efficacy and feasibility of cyclophosphamide combined with intermediate-dose or high-dose cytarabine for relapsed and refractory acute myeloid leukemia (AML). J.Cancer Res.Clin.Oncol. 140(8): 1391-1397.
Schnetzke U, Schrenk K, Spies-Weisshart B, Kunert C, Hochhaus A and Scholl S. 2014. Different clones of acute leukemia after successful treatment of Hodgkin’s disease. Ann.Hematol. 93(12): 2077-2079.
Publications prior to 2013
Schrenk KG, Krokowski M, Feller AC, Mügge L-O, Oelzner P, Wolf P, Hochhaus A and Neumann T. 2013.Clonal T-LGL population mimicking leukemia in Felty’s Syndrome- part of a continuous spectrum of T-LGL proliferations? Ann.Hematol.92(7):985-987.
Kudo NR, Wassmann K, Anger M, Schuh M, Wirth KG, Xu H, Helmhart W, Kudo H, Mckay M, Maro B, Ellenberg J, de Boer P and Nasmyth K. 2006. Resolution of chiasmata in oocytes requires separase-mediated proteolysis. Cell 126(1): 135-146.
Wirth KG, Wutz G, Kudo NR Desdouets C, Zetterberg A, Taghybeeglu S, Seznec J, Ducos GM, Ricci R, Firnberg N, Peters JM and Nasmyth K. 2006. Separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression. J. Cell Biol. 172 (6): 847-860.
Wirth KG, Ricci R, Giménez-Abián JF, Taghybeeglu S, Kudo NR, Jochum W, Vasseur-Cognet M and Nasmyth K. 2004. Loss of the anaphase-promoting complex in quiescent cells causes unscheduled hepatocyte proliferation. Genes Dev. 18(1): 88-98.
Prof. Dr. med. Marie von Lilienfeld-Toal (Group leader)
Fon: +49 3641 9-324210
Fax: +49 3641 9-324657
Laboratory in
Leibniz Institut für Naturstoffforschung und Infektionsbiologie
Hans-Knöll-Institut
Beutenbergstr. 11a
07745 Jena
Homepage: http://www.leibniz-hki.de/de/infektionen-in-der-haematologieonkologie.html
Dr. Annamaria Brioli, Dr. rer. nat. Susann Hartung, Dr. rer. nat. Susanne Jahreis, Maria Magdalena Rüthrich
Ava Kiesewetter
Jana Kalkreuth, Julia Kurrek, Stephanie Kurze, Katharina Meckel, Ellen Ritter, Verena Schlüter, Maria Schuwirth, Mai Hoang
Infections are the major cause of treatment-related mortality in patients with malignant diseases. This is commonly believed to be due to a profound immunosuppression, which makes patients susceptible to opportunistic infections. Invasive fungal infections are a good example for such opportunistic infections, which almost never occur in healthy individuals and which are exceptionally difficult to diagnose. In addition, treatment of invasive fungal infection is often toxic and not very successful. For these reasons, invasive fungal infections in patients with hematological malignancies have a very high mortality rate.
Besides opportunistic infections, cancer patients are at risk of common infections, which often take a more severe clinical course than in healthy individuals. This is believed to be the case with infections concerning respiratory viruses like influenza or adenovirus. We aim at understanding the pathogenesis and clinical course of some of these infections with the goal to improve diagnostics and clinical treatment of these patients.
2019
Dimitriou V, Biehl LM, Hamprecht A, Vogel W, Dörfel D, Peter S, Schafhausen P, Rohde H, von Lilienfeld-Toal M, Klassert TE, Slickers P, Ehricht R, Slevogt H, Christ H, Hellmich M, Farowski F, Tsakmaklis A, Higgins PG, Seifert H, Vehreschild MJGT. Controlling intestinal colonization of high-risk haematology patients with ESBL-producing Enterobacteriaceae: a randomized, placebo-controlled, multicentre, Phase II trial (CLEAR). J Antimicrob Chemother. 2019 Jul 1;74(7):2065-2074. doi: 10.1093/jac/dkz124. PubMed PMID: 31220256.
von Lilienfeld-Toal M, Wagener J, Einsele H, Cornely OA, Kurzai O. Invasive Fungal Infection. Dtsch Arztebl Int. 2019 Apr 19;116(16):271-278. doi: 10.3238/arztebl.2019.0271. PubMed PMID: 31159914; PubMed Central PMCID: PMC6549129.
Roth M, Daas L, Renner-Wilde A, Cvetkova-Fischer N, Saeger M, Herwig-Carl M, Matthaei M, Fekete A, Kakkassery V, Walther G, von Lilienfeld-Toal M, Mertens C, Lenk J, Mehlan J, Fischer C, Fuest M, Kroll S, Bayoudh W, Viestenz A, Frings A, MacKenzie CR, Messmer EM, Seitz B, Kurzai O, Geerling G. [The German keratomycosis registry : Initial results of a multicenter survey]. Ophthalmologe. 2019 Feb 27. doi: 10.1007/s00347-019-0871-9. [Epub ahead of print] German. PubMed PMID: 30810837.
Kochanek M, Schalk E, von Bergwelt-Baildon M, Beutel G, Buchheidt D, Hentrich M, Henze L, Kiehl M, Liebregts T, von Lilienfeld-Toal M, Classen A, Mellinghoff S, Penack O, Piepel C, Böll B. Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2019 May;98(5):1051-1069. doi: 10.1007/s00277-019-03622-0. Epub 2019 Feb 22. Review. PubMed PMID: 30796468; PubMed Central PMCID: PMC6469653.
Brioli A, Klaus M, Sayer H, Scholl S, Ernst T, Hilgendorf I, Scherag A, Yomade O, Schilling K, Hochhaus A, Mügge LO, von Lilienfeld-Toal M. The risk of infections in multiple myeloma before and after the advent of novel agents: a 12-year survey. Ann Hematol. 2019 Mar;98(3):713-722. doi: 10.1007/s00277-019-03621-1. Epub 2019 Jan 24. PubMed PMID: 30680505.
Hartung S, Rauh C, Hoang TNM, Jahreis S, Wagner K, Macheleidt J, Brakhage AA, Rummler S, Hochhaus A, von Lilienfeld-Toal M. Fast and Quantitative Evaluation of Human Leukocyte Interaction with Aspergillus fumigatus Conidia by Flow Cytometry. Cytometry A. 2019 Mar;95(3):332-338. doi: 10.1002/cyto.a.23653. Epub 2018 Nov 19. PubMed PMID: 30450827.
Hütter-Krönke ML, Fiedler W, Kündgen A, Krauter J, von Lilienfeld-Toal M, Döhner H, Schlenk RF. Continuous high dosing of lenalidomide in relapsed, refractory or older newly diagnosed acute myeloid leukemia patients not suitable for other treatment options - results from a phase I study. Haematologica. 2019 Feb;104(2):e63-e64. doi: 10.3324/haematol.2018.199794. Epub 2018 Aug 31. PubMed PMID: 30171028; PubMed Central PMCID: PMC6355481.
2018
Ruhnke M, Behre G, Buchheidt D, Christopeit M, Hamprecht A, Heinz W, Heussel CP, Horger M, Kurzai O, Karthaus M, Löffler J, Maschmeyer G, Penack O, Rieger C, Rickerts V, Ritter J, Schmidt-Hieber M, Schuelper N, Schwartz S, Ullmann A, Vehreschild JJ, von Lilienfeld-Toal M, Weber T, Wolf HH. Diagnosis of invasive fungal diseases in haematology and oncology: 2018 update of the recommendations of the infectious diseases working party of the German society for hematology and medical oncology (AGIHO). Mycoses. 2018 Nov;61(11):796-813. doi: 10.1111/myc.12838. Epub 2018 Sep 3. Review. PubMed PMID: 30098069.
Jahreis S, Böttcher S, Hartung S, Rachow T, Rummler S, Dietl AM, Haas H, Walther G, Hochhaus A, von Lilienfeld-Toal M. Human MAIT cells are rapidly activated by Aspergillus spp. in an APC-dependent manner. Eur J Immunol. 2018 Oct;48(10):1698-1706. doi: 10.1002/eji.201747312. Epub 2018 Aug 13. PubMed PMID: 30059139.
von Lilienfeld-Toal M, Maschmeyer G. Challenges in Infectious Diseases for Haematologists. Oncol Res Treat. 2018;41(6):406-410. doi: 10.1159/000487439. Epub 2018 May 7. Review. PubMed PMID: 29734194.
Rieger CT, Liss B, Mellinghoff S, Buchheidt D, Cornely OA, Egerer G, Heinz WJ, Hentrich M, Maschmeyer G, Mayer K, Sandherr M, Silling G, Ullmann A, Vehreschild MJGT, von Lilienfeld-Toal M, Wolf HH, Lehners N; German Society of Hematology and Medical Oncology Infectious Diseases Working Group (AGIHO). Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors-Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). Ann Oncol. 2018 Jun 1;29(6):1354-1365. doi: 10.1093/annonc/mdy117. PubMed PMID: 29688266; PubMed Central PMCID: PMC6005139.
2017
Mellinghoff SC, Panse J, Alakel N, Behre G, Buchheidt D, Christopeit M, Hasenkamp J, Kiehl M, Koldehoff M, Krause SW, Lehners N, von Lilienfeld-Toal M, Löhnert AY, Maschmeyer G, Teschner D, Ullmann AJ, Penack O, Ruhnke M, Mayer K, Ostermann H, Wolf HH, Cornely OA. Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO). Ann Hematol. 2018 Feb;97(2):197-207. doi: 10.1007/s00277-017-3196-2. Epub 2017 Dec 7. Review. PubMed PMID: 29218389; PubMed Central PMCID: PMC5754425.
Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, Karthaus M, Link H, Mahlberg R, Neumann S, Ostermann H, Penack O, Ruhnke M, Sandherr M, Schiel X, Vehreschild JJ, Weissinger F, Maschmeyer G. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2017 Nov;96(11):1775-1792. doi: 10.1007/s00277-017-3098-3. Epub 2017 Aug 30. Review. PubMed PMID: 28856437; PubMed Central PMCID: PMC5645428.
Walther G, Stasch S, Kaerger K, Hamprecht A, Roth M, Cornely OA, Geerling G, Mackenzie CR, Kurzai O, von Lilienfeld-Toal M. Fusarium Keratitis in Germany. J Clin Microbiol. 2017 Oct;55(10):2983-2995. doi: 10.1128/JCM.00649-17. Epub 2017 Jul 26. PubMed PMID: 28747368; PubMed Central PMCID: PMC5625384.
Rachow T, Schlüter V, Bremer-Streck S, Lindig U, Scholl S, Schlattmann P, Kiehntopf M, Hochhaus A, von Lilienfeld-Toal M. Measurement of piperacillin plasma concentrations in cancer patients with suspected infection. Infection. 2017 Oct;45(5):629-636. doi: 10.1007/s15010-017-1026-z. Epub 2017 May 17. PubMed PMID: 28516432.
Biehl LM, Bertz H, Bogner J, Dobermann UH, Kessel J, Krämer C, Lemmen S, von Lilienfeld-Toal M, Peter S, Pletz MW, Rohde H, Schmiedel S, Schubert S, Ullmann AJ, Fätkenheuer G, Vehreschild MJGT. Screening and contact precautions - A survey on infection control measures for multidrug-resistant bacteria in German university hospitals. Antimicrob Resist Infect Control. 2017 Apr 13;6:37. doi: 10.1186/s13756-017-0191-2. eCollection 2017. PubMed PMID: 28413631; PubMed Central PMCID: PMC5390437.
Brioli A, Mügge LO, Hochhaus A, Von Lilienfeld-Toal M. Safety issues and management of toxicities associated with new treatments for multiple myeloma. Expert Rev Hematol. 2017 Mar;10(3):193-205. doi: 10.1080/17474086.2017.1284584.
Epub 2017 Jan 27. Review. PubMed PMID: 28116920.
2016
Hermann B, Lehners N, Brodhun M, Boden K, Hochhaus A, Kochanek M, Meckel K, Mayer K, Rachow T, Rieger C, Schalk E, Weber T, Schmeier-Jürchott A, Schlattmann P, Teschner D, von Lilienfeld-Toal M. Influenza virus infections in patients with malignancies -- characteristics and outcome of the season 2014/15. A survey conducted by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO). Eur J Clin Microbiol Infect Dis. 2017 Mar;36(3):565-573. doi: 10.1007/s10096-016-2833-3. Epub 2016 Nov 12. PubMed PMID: 27838792; PubMed Central PMCID: PMC5309266.
von Lilienfeld-Toal M, Berger A, Christopeit M, Hentrich M, Heussel CP, Kalkreuth J, Klein M, Kochanek M, Penack O, Hauf E, Rieger C, Silling G, Vehreschild M, Weber T, Wolf HH, Lehners N, Schalk E, Mayer K. Community acquired respiratory virus infections in cancer patients-Guideline on diagnosis and management by the Infectious Diseases Working Party of the German Society for haematology and Medical Oncology. Eur J Cancer. 2016 Nov;67:200-212. doi: 10.1016/j.ejca.2016.08.015. Epub 2016 Sep 25. Review. PubMed PMID: 27681877.
Rachow T, Dornaus S, Sayer HG, Hermann B, Hochhaus A, von Lilienfeld-Toal M. Case report: false positive elevated serum-galactomannan levels after autologous hematopoietic stem cell transplantation caused by oral nutritional supplements. Clin Case Rep. 2016 Apr 12;4(5):505-8. doi: 10.1002/ccr3.516. eCollection 2016 May. PubMed PMID: 27188260; PubMed Central PMCID: PMC4856246.
2015
Richter ME, Neugebauer S, Engelmann F, Hagel S, Ludewig K, La Rosée P, Sayer HG, Hochhaus A, von Lilienfeld-Toal M, Bretschneider T, Pausch C, Engel C, Brunkhorst FM, Kiehntopf M (2015) Biomarker candidates for the detection of an infectious etiology of febrile neutropenia. Infection [Epub ahead of print]
Sandherr M, Hentrich M, von Lilienfeld-Toal M, Massenkeil G, Neumann S, Penack O, Biehl L, Cornely OA (2015) Antiviral prophylaxis in patients with solid tumours and haematological malignancies--update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). Ann Hematol. 94(9):1441-50.
Schrenk KG, Schnetzke U, Stegemann K, von Lilienfeld-Toal M, Hochhaus A, Scholl S (2015) Efficacy of antifungal prophylaxis with oral suspension posaconazole during induction chemotherapy of acute myeloid leukemia. J Cancer Res Clin Oncol. 141(9):1661-8
Mayer K, Hahn-Ast C, Mückter S, Schmitz A, Krause S, Felder L, Bekeredjian-Ding I, Molitor E, Brossart P, von Lilienfeld-Toal M (2015) Comparison of antibiotic prophylaxis with cotrimoxazole/colistin (COT/COL) versus ciprofloxacin (CIP) in patients with acute myeloid leukemia. Support Care Cancer. 23(5):1321-9.
Schnetzke U, Spies-Weisshart B, Yomade O, Fischer M, Rachow T, Schrenk K, Glaser A, von Lilienfeld-Toal M, Hochhaus A, Scholl S (2015) Polymorphisms of Toll-like receptors (TLR2 and TLR4) are associated with the risk of infectious complications in acute myeloid leukemia. Genes Immun. 16(1):83-8
2014
Vehreschild MJ, Hamprecht A, Peterson L, Schubert S, Häntschel M, Peter S, Schafhausen P, Rohde H, Lilienfeld-Toal MV, Bekeredjian-Ding I, Libam J, Hellmich M, Vehreschild JJ, Cornely OA, Seifert H (2014) A multicentre cohort study on colonization and infection with ESBL-producing Enterobacteriaceae in high-risk patients with haematological malignancies. J Antimicrob Chemother. 69(12):3387-92.
Busch A, Zeh D, Janzen V, Mügge LO, Wolf D, Fingerhut L, Hahn-Ast C, Maurer O, Brossart P, von Lilienfeld-Toal M (2014) Treatment with lenalidomide induces immunoactivating and counter-regulatory immunosuppressive changes in myeloma patients. Clin Exp Immunol 177(2), 439-453.
Penack O, Becker C, Buchheidt D, Christopeit M, Kiehl M, von Lilienfeld-Toal M, Hentrich M, Reinwald M, Salwender H, Schalk E, Schmidt-Hieber M, Weber T, Ostermann H (2014) Management of sepsis in neutropenic patients: 2014 updated guidelines from the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO). Ann Hematol 93(7), 1083-1095.
Schwab KS, Hahn-Ast C, Heinz WJ, Germing U, Egerer G, Glasmacher A, Leyendecker C, Marklein G, Nellessen CM, Brossart P, von Lilienfeld-Toal M (2014) Tigecycline in febrile neutropenic patients with haematological malignancies: a retrospective case documentation in four university hospitals. Infection 42(1), 97-9104.
2013
Feldmann G, Brossart P, von Lilienfeld-Toal M (2013) Transient and fully reversible leukocytosis in a myelodysplastic syndrome patient upon initiation of azacitidine treatment. Ann Hematol 92(11), 1577-1579.
Feldmann G, Brossart P, Zipfel M, von Lilienfeld-Toal M (2013) Mixed response to ipilimumab in a melanoma patient with brain metastases: case report and review of the literature. Case Rep Oncol 6(1), 229-235.
Gaidzik VI, Schlenk RF, Paschka P, Stölzle A, Späth D, Kuendgen A, von Lilienfeld-Toal M, Brugger W, Derigs HG, Kremers S, Greil R, Raghavachar A, Ringhoffer M, Salih HR, Wattad M, Kirchen HG, Runde V, Heil G, Petzer AL, Girschikofsky M, Heuser M, Kayser S, Goehring G, Teleanu MV, Schlegelberger B, Ganser A, Krauter J, Bullinger L, Döhner H, Döhner K (2013) Clinical impact of DNMT3A mutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG). Blood 121(23), 4769-4777.
Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U (2013) Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 369(2), 111-121.
Mayer K, Kapelle M, Kaeferstein A, Weßling M, Bekeredjian-Ding I, Leutner C, von Lilienfeld-Toal M, Brossart P, Wolf D (2013) Successful management of Candida krusei monoarthritis after allo-SCT. Bone Marrow Transplant 48(12), 1585-1586.
Neumann S, Krause SW, Maschmeyer G, Schiel X, von Lilienfeld-Toal M (2013) Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors: guidelines of the Infectious Diseases Working Party (AGIHO) of the DGHO. Ann Hematol 92(4), 433-442.
Paschka P, Du J, Schlenk RF, Gaidzik VI, Bullinger L, Corbacioglu A, Späth D, Kayser S, Schlegelberger B, Krauter J, Ganser A, Köhne CH, Held G, von Lilienfeld-Toal M, Kirchen H, Rummel M, Götze K, Horst HA, Ringhoffer M, Lübbert M, Wattad M, Salih HR, Kündgen A, Döhner H, Döhner K (2013) Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG). Blood 121(1), 170-177.
Bundesministerium für Bildung und Forschung
José-Carreras-Stiftung
Interdisziplinäres Zentrum für Klinische Forschung
