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Mertelsmann studied medicine at the University of Göttingen 1966–68. He was a doctoral candidate at the Max Planck Institute for Experimental Medicine at Heinrich Matthaei in Göttingen 1966–68. He continued his medical education at the School of Medicine King's College London and at the Columbia-Presbyterian Medical Center, New York 1968–78. After graduating from Hamburg University Medical School and receiving his MD degree, he became Research Fellow at the Department of Developmental Hematopoiesis and received a special fellowship in Hematology and Clinical Oncology at Memorial Sloan-Kettering Cancer Center (MSKCC), 1976–78. There he contributed to the isolation of the blood stimulating growth factor G-CSF, which leads to a faster recovery of white blood cells after chemotherapy and radiation therapy protecting patients better against severe infections. From 1978 to 86 he was clinical assistant physician at MSKCC, then assistant attending physician and associate attending physician at the Memorial Hospital of Sloan-Kettering Cancer Center. He was promoted from assistant professor of medicine to associate professor of medicine at Cornell University, New York. In 1985, he returned to Germany and was appointed professor and head of the 3rd Medical Clinic Hematology and Oncology at the University of Mainz, Germany, University Medical Center. 1989 he accepted a professorship at the University of Freiburg. At Freiburg University Medical Center he became the director of the Department for Medicine I, Oncology, Hematology and Stem Cell Transplantation. He retired in 2012.[2]
During his career Mertelsmann recruited and promoted young scientists. Several leading positions at universities and in the industry were occupied with former team members of Mertelsmann. In 2008 he founded the International Master Program in Biomedical Sciences,[3] a cooperation of the universities of Freiburg and Buenos Aires, educating and training international master students in biomedicine. In 2014 he initiated the foundation of the journal JOSHA,[4] a novel internet platform to access the broad diversity of important discoveries and creativity in the fields of science, humanities and arts. Mertelsmann published more than 400 articles in medical journals.[citation needed]
Scientific contribution
Molecular and cellular mechanisms of malignancy- First description of a human RNA polymerase
After discovery of the genetic code by Heinrich Matthaei and Marshall Nirenberg (1962), Mertelsmann began his research for his medical doctorate as a medical student in Heinrich Matthaei's Laboratory at the Max-Planck-Institute for experimental Medicine in Göttingen, Germany, demonstrating and characterizing for the first time a human RNA-Polymerase.[5] Since nucleic acid synthesis is an important target for chemotherapeutic agents, he subsequently investigated in his team together with various colleagues, DNA-Polymerases, especially terminal deoxynucleotidyl transferase (TdT), and RNA-Polymerases as diagnostic and prognostic markers in leukemias and lymphomas.[6]
Studies of the Pathophysiology and Molecular Biology of Cancer Cells
The "Plasticity" of hematopoieticstem cells (HSC), i.e. the differentiation of HSC into cells of other organs,[7] was intensively studied with Alexandros Spyridonidis[8] in patients after allogeneic bone marrow transplantation. These studies demonstrated conclusively, that this phenomenon can be observed in these patients, but is a rare event. Molecular mechanisms of B-cellneoplasias[9][10] were investigated together with Binder, Trepel and Dierks, the pathogenic significance of granulocytes in Graft-versus-host disease with Zeiser and his colleagues.[11]
Clinical Significance of the Leukemia Phenotype
As a member of the clinical (Director Bayard Clarkson) and laboratory teams (Director Malcolm A.S. Moore), he carried out a systematic analysis of all patients with acute myeloid leukemia (AML) treated at MSKCC, defining the prognostic and predictive parameters of cell cytology, cell growth in vitro and enzymatic markers.[12][13] By using all techniques available at the time for phenotypic characterization of leukemia cells, he was successful in discovering and describing novel subentities of acute leukemias.[14][15]
New therapeutic Modalities
In Cooperation with Karl Welte and his colleagues at MSKCC the purification and molecular and biological characterization of cytokines, important regulators of cell division, differentiation and migration, were the focus of his work in the following years at MSKCC. Interleukin-2[16] as well as G-CSF[17] were purified to homogeneity, First translational and clinical studies of cytokines followed.[18] Since experiments in murine models demonstrated that local production by gene transduced cells produced a stronger and more specific immune response than a systemic application, e.g. of Interleukin-2, this strategy was also pursued by his group in Phase I clinical trials.[19][20][21] These studies contributed to the later, successful clinical implementation of gene therapy for this and other indications.[citation needed]
Clinical Studies
In clinical trials for patients with leukemias and lymphomas at the MSKCC[22] and subsequently in German and European clinical trial groups,[23][24] new therapeutic concepts were studied including classical chemotherapies as well as novel therapeutic strategies.[25][26] For some rare, generally lethal cancers, the innovative use of rapidly recycling classical chemotherapy combinations followed by immediate High Dose Chemotherapy with HSC transplantation, led to long term remission and probably cures, which had not been seen with other therapies and in historical controls.[27]
As clinical oncologist Mertelsmann also search for novel strategies to not only prolong life, but to increase quality of life. The systematic development of aerobic training programs for cancer patients undergoing chemotherapy and bone morrow transplantation[28] was highly successful and is now being used in many cancer centers worldwide.[citation needed]
Accusation of scientific misconduct
Mertelsmann was involved in a scientific misconduct affair in 1997. The complaint focussed on the falsification of laboratory data. An investigation commission did not prove the active participation of Mertelsmann.[29]
Academic memberships
Mertelsmann is or was member of many international scientific organizations or journals, among them many years at the journals European Journal of Cancer and Annals of Hematology. He is a foundation member of the Comprehensive Cancer Center Freiburg (CCCF), Initiator and director of the International Biomedical Exchange Program (IMEP), founder of the ARGER-Foundation,[30] editor of the SRC-SDARF-UJDRF Joint Programme in Stem Cell Research, Stockholm and president of the International Association for Comparative Research on Leukemia and related Diseases (IACRLD).[citation needed]
^R. Mertelsmann: Purification and some properties of a soluble DNA-dependent. RNA polymerase from nuclei of human placenta. In: Eur. J. Biochem. 1969 Jun;9(3), S. 311–318. PMID5795512
^R. Mertelsmann, B. Koziner, D. A. Filippa, E. Grossbard, G. Incefy, M. A. Moore, B. D. Clarkson: Clinical significance of TdT, cell surface markers and CFU-C in 297 patients with hematopoietic neoplasias. In: Haematol Blood Transfus. 1979;23, S. 131–138. PMID317470. Prof. em. Dr. Drs. h.c. Roland Mertelsmann
^R. Mertelsmann: Plasticity of bone marrow-derived stem cells. In: J Hematother Stem Cell Res. 2000 Dec;9(6), S. 957–960. Review. PMID11177610
^A. Spyridonidis, R. Mertelsmann, J. Finke: Hematopoietic stem cell transplantation: more than just hematopoietic? In: J Cancer Res Clin Oncol. 2004 Mar;130(3), S. 127–134. Epub 2004 Jan 16. Review. PMID14727105
^M. Binder, F. Müller, M. Frick, C. Wehr, F. Simon, B. Leistler, H. Veelken, R. Mertelsmann, M. Trepel: CLL B-cell receptors can recognize themselves: alternative epitopes and structural clues for autostimulatory mechanisms in CLL. In: Blood. 2013 Jan 3;121(1), S. 239–241. doi:10.1182/blood-2012-09-454439. PMID23287626
^C. Dierks, J. Grbic, K. Zirlik, R. Beigi, N. P. Englund, G. R. Guo, H. Veelken, M. Engelhardt, R. Mertelsmann, J. F. Kelleher, P. Schultz, M. Warmuth: Essential role of stromally induced hedgehog signaling in B-cell malignancies. In: Nat Med. 2007 Aug;13(8), S. 944–951. Epub 2007 Jul 15. PMID17632527.
^L. Schwab, L. Goroncy, S. Palaniyandi, S. Gautam, A. Triantafyllopoulou, A. Mocsai, W. Reichardt, F. J. Karlsson, S. V. Radhakrishnan, K. Hanke, A. Schmitt-Graeff, M. Freudenberg, F. D. von Loewenich, P. Wolf, F. Leonhardt, N. Baxan, D. Pfeifer, O. Schmah, A. Schönle, S. F. Martin, R. Mertelsmann, J. Duyster, J. Finke, M. Prinz, P. Henneke, H. Häcker, G. C. Hildebrandt, G. Häcker, R. Zeiser: Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. In: Nat Med. 2014 Jun;20(6), S. 648–654. doi:10.1038/nm.3517. Epub 2014 May 18. PMID24836575
^R. Mertelsmann, M. A. Moore, B. Clarkson: Leukemia cell phenotype and prognosis: an analysis of 519 adults with acute leukemia. In: Blood Cells. 1982;8(3), S. 561–583. PMID6984348
^R. Mertelsmann, H. Tzvi Thaler, L. To, T. S. Gee, S. McKenzie, P. Schauer, A. Friedman, Z. Arlin, C. Cirrincione, B. Clarkson: Morphological classification, response to therapy, and survival in 263 adult patients with acute nonlymphoblastic leukemia. In: Blood. 1980 Nov;56(5), S. 773–781. PMID6932977.
^N. Ciobanu, M. Andreeff, B. Safai, B. Koziner, R. Mertelsmann: Lymphoblastic neoplasia in a homosexual patient with Kaposi’s sarcoma. In: Ann Intern Med. 1983 Feb;98(2), S. 151–155. PMID6572044.
^R. Mertelsmann, B. Koziner, R. Ralph, D. Filippa, S. McKenzie, Z. A. Arlin, T. S. Gee, M. A. Moore, B. D. Clarkson: Evidence for distinct lymphocytic and monocytic populations in a patient with terminal transferase—positive acute leukemia. In: Blood. 1978 Jun;51(6), S. 1051–1056. PMID274159
^K. Welte, C. Y. Wang, R. Mertelsmann, S. Venuta, S. P. Feldman, M. A. Moore: Purification of human interleukin 2 to apparent homogeneity and its molecular heterogeneity. In: J Exp Med. 1982 Aug 1;156(2), S. 454–464. PMID6980256PMC2186775
^K. Welte, E. Platzer, L. Lu, J. L. Gabrilove, E. Levi, R. Mertelsmann, M. A. Moore: Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor. In: Proc Natl Acad Sci U S A. 1985 Mar;82(5), S. 1526–1530. PMID3871951PMC397296
^R. Mertelsmann, K. Welte, C. Sternberg, R. O'Reilly, M. A. Moore, B. D. Clarkson, H. F. Oettgen: Treatment of immunodeficiency with interleukin-2: initial exploration. In: J Biol Response Mod. 1984 Oct;3(5), S. 483–490. PMID6334136
^H. Glimm, K. Flügge, D. Möbest, V. M. Hofmann, J. Postmus, R. Henschler, W. Lange, J. Finke, H. P. Kiem, G. Schulz, F. Rosenthal, R. Mertelsmann, C. von Kalle: Efficient serum-free retroviral gene transfer into primitive human hematopoietic progenitor cells by a defined, high-titer, nonconcentrated vector-containing medium. In: Hum Gene Ther. 1998 Apr 10;9(6), S. 771–778. PMID9581900.
^H. Veelken, A. Mackensen, M. Lahn, G. Köhler, D. Becker, B. Franke, U. Brennscheidt, P. Kulmburg, F. M. Rosenthal, H. Keller, J. Hasse, W. Schultze-Seemann, E. H. Farthmann, R. Mertelsmann, A. Lindemann: A phase-I clinical study of autologous tumor cells plus interleukin-2-gene-transfected allogeneic fibroblasts as a vaccine in patients with cancer. In: Int J Cancer. 1997 Jan 27;70(3), S. 269–277. PMID9033626
^G. Stingl, E. B. Brŏcker, R. Mertelsmann, K. Wolff, S. Schreiber, E. Kămpgen, A. Schneeberger, W. Dummer, U. Brennscheid, H. Veelken, M. L. Birnstiel, K. Zatloukal, W. Schmidt, G. Maass, E. Wagner, M. Baschle, M. Giese, E. R. Kempe, H. A. Weber, T. Voigt: Phase I study to the immunotherapy of metastatic malignant melanoma by a cancer vaccine consisting of autologous cancer cells transfected with the human IL-2 gene. In: Hum Gene Ther. 1996 Mar 1;7(4), S. 551–563. PMID8800750
^R. Mertelsmann, R. L. Drapkin, T. S. Gee, S. Kempin, S. Passe, H. T. Thaler, Z. Arlin, M. Dowling, P. Dufour, S. McKenzie, L. To, E. Comacho, H. F. Oettgen, J. H. Burchenal, B. Clarkson: Treatment of acute nonlymphocytic leukemia in adults: response to 2,2-anhydro-1-B-D-arabinofuranosyl-5-fluorocytosine and thioguanine on the L-12 protocol. In: Cancer. 1981 Nov 15;48(10), S. 2136–2142. PMID6170414
^M. Pfreundschuh, J. Schubert, M. Ziepert, R. Schmits, M. Mohren, E. Lengfelder, M. Reiser, C. Nickenig, M. Clemens, N. Peter, C. Bokemeyer, H. Eimermacher, A. Ho, M. Hoffmann, R. Mertelsmann, L. Trümper, L. Balleisen, R. Liersch, B. Metzner, F. Hartmann, B. Glass, V. Poeschel, N. Schmitz, C. Ruebe, A. C. Feller, M. Loeffler: German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). In: Lancet Oncol. 2008 Feb;9(2), S. 105–116. doi:10.1016/S1470-2045(08)70002-0. Epub 2008 Jan 15. PMID18226581
^O. Determann, E. Hoster, G. Ott, H. Wolfram Bernd, C. Loddenkemper, M. Leo Hansmann, T. E. Barth, M. Unterhalt, W. Hiddemann, M. Dreyling, W. Klapper: European Mantle Cell Lymphoma Network and the German Low Grade Lymphoma Study Group. Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group. In: Blood. 2008 Feb 15;111(4), S. 2385–2387. Epub 2007 Dec 12. PMID18077791
^H. P. Koeffler, D. Heitjan, R. Mertelsmann, J. E. Kolitz, P. Schulman, L. Itri, P. Gunter, E. Besa: Randomized study of 13-cis retinoic acid v placebo in the myelodysplastic disorders. In: Blood. 1988 Mar;71(3), S. 703–708. PMID3278754. 309: W. Hiddemann, H. Kreutzmann, K. Straif, W. D. Ludwig, R. Mertelsmann, M. Planker, R. Donhuijsen-Ant, E. Lengfelder, Z. Arlin, T. Büchner: High-dose cytosine arabinoside in combination with mitoxantrone for the treatment of refractory acute myeloid and lymphoblastic leukemia. In: Semin Oncol. 1987 Jun;14(2 Suppe 1), S. 73–77. PMID3473685
^E. J. Gold, R. H. Mertelsmann, L. M. Itri, T. Gee, Z. Arlin, S. Kempin, B. Clarkson, M. A. Moore: Phase I clinical trial of 13-cis-retinoic acid in myelodysplastic syndromes. In: Cancer Treat Rep. 1983 Nov;67(11), S. 981–986. PMID6580071
^L. Houet, I. Möller, M. Engelhardt, G. Köhler, H. Schmidt, D. Herchenbach, M. Schnitzler, A. Schmitt-Graeff, A. A. Jungbluth, R. Mertelsmann, B. Rumstadt, C. F. Waller: Long-term remission after CD34+-selected PBSCT in a patient with advanced intra-abdominal desmoplastic small round-cell tumor. In: Bone Marrow Transplant. 2010 Apr;45(4), S. 793–795. doi:10.1038/bmt.2009.226. Epub 2009 Aug 31. PMID19718066PMC3147145
^F. Dimeo, H. Bertz, J. Finke, S. Fetscher, R. Mertelsmann, J. Keul: An aerobic exercise program for patients with haematological malignancies after bone marrow transplantation. In: Bone Marrow Transplant. 1996 Dec;18(6), S. 1157–1160. PMID8971388.
