Hämatologie und Bluttransfusion

Transkript

1 Haematology and Blood Transfusion Hämatologie und Bluttransfusion Edited by H. Heirnpel, Ulrn. D. Huhn, München C. Mueller-Eckhardt, Gießen G. Ruhenstroth-Bauer, München

2 Modern Trends in Human Leukemia IV Latest Results in Clinical and Biological Research Including Pediatric Oncology Organized on behalf of the Deutsche Gesellschaft für Hämatologie und Onkologie and the Deutsches Krebsforschungszentrum. Wilsede, June 16-19, 1980 Wilsede Joint Meeting on Pediatric Oncology I Hamburg, June 20/21, 1980 Editedby R. Neth, R. C. Gallo, T. Graf, K. Mannweiler and K. Winkler With 252 Figures and 118 Tables Springer-Verlag Berlin Heidelberg NewYork 1981

3 Dr. Rolf Neth, Universitäts-Kinderklinik, Molekularbiologisch-hämatologische Arbeitsgruppe, Martinistraße 52, D-2000 Hamburg 20, Federal Republic of Germany Dr. Robert C. Gallo, National Cancer Institute, Laboratory of Tumor Cell Biology, Bethesda, Maryland 20014, USA Dr. Thomas Graf, Institut für Virusforschung, Im Neuenheimer Feld 280, D-6900 Heidelberg 1, Federal Republic of Germany Dr. Klaus Mannweiler, Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Martinistraße 52, D-2000 Hamburg 20, Federal Republic of Germany Dr. Kurt Winkler, Universitäts-Kinderklinik, Abteilung für Haematologie und Onkologie, Martinistr. 52, D-2000 Hamburg 20, Federal Republic of Germany Supplement to BLUT - Journal Experimental and Clinical Hematology Organ of the Deutsche Gesellschaft für Hämatologie I1nd Onkologie der Deutschen Gesellschaft für Bluttransfusion und Immunohämatologie and of the Osterreichischen Gesellschaft für Hämatologie und Onkologie ISBN-13: e-isbn-!3: DOI: I / This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under 54 of the German Copyright Lawwhere copies are made for other than private use a fee is payable to "Verwertungsgesellschaft Wort", Munich. Springer-Verlag Berlin Heidelberg 1981 The use of registered names, trademarks etc. in this publication does not imply even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. 2127/3321/543210

4 Scientilic Organisation of the Sessions Clinical Aspects Frei, Emil II!, Sidney Farber Cancer Institute, 44, Binney Street, Boston, MA 02115, USA Lister, Andrew, Dept. Medical Oncology, St. Bartholomew's Hospital, West Smithfield, London ECIA7BE, U.K. Cytogenetic and Lymphomas Kaplan, Henry S., Dept. Radiology, Cancer Biology Research Laboratory, Stanford University Medical School, Stanford CA 94305, USA Klein, George, Dept. Tumor Biology, Karolinska Institutet 104 Stockholm 60, Sweden Cell Biology Greaves, Mel F., Imperial Cancer Research Fund Laboratories P.O. Box 123, Lincoln's Inn Fields, London WC2A3PX, u.k. Moore, MaJcolm, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA Immunology Eichmann, Klaus, Krebsforschungszentrum - Immunologie, Im Neuenheim er Feld 280, 6900 Heidelberg, West Germany Mitchison, Nicholas Avrion, Tumor Immunology Unit, University College London, Gower Street, London WCIE6BT, U.K. Virology and Molecular Biology Duesberg, Peter, Dept. Molecular Biology, WendeIl M. Stanley Hall, University of California, Berkeley, CA 94720, USA Gallo, Robert c., National Cancer Institute, Bethesda, MD 20014, USA Wilsede Joint Meeting on Pediatric Oncology I Kabisch, Hartmut, Universitätskinderklinik, Abt. für Hämatologie und Onkologie, Martinistr. 52, 2000 Hamburg 20, West-Germany Winkler, Kurt, Universitätskinderklinik, Abt. für Hämatologie und Onkologie, Martinistr. 52, 2000 Hamburg 20, West-Germany v

5 Contents Participants of the Meeting XV Wilsede Scholarship Holders XIX Preface XXI Acknowledgement... XXV Frederick Stohlman Jr. Memorial Lecture Klein, G.: The Relative Role of Viral Transformation and Specific Cytogenetic Changes in the Development of Murine and Human Lymphomas... 3 Kaplan, H. S.: On the Biology and Immunology of Hodgkin's Disease Clinical Aspects Rowley, J. D.: Chromosome Studies in Children and Adults with Leukemia Georgii, A., Thiele, J., Vykoupil, K.-F.: Myelqid Dysplasia: the Histopathology of Preleukemia Lister, T. A., Johnson, S. A. N., Bell, R., Henry, G., Malpas, J. S.: Progress in Acute Myelogenous Leukemia Mayer, R. J., Weinstein, H. J., Rosenthai, D. S., Coral, F,'S., Nathan, D. G., Frei, E. III.: VAPA10 : A TreatmenfProgram for Acute Myelocytic Leukemia Preisler, H. D.: Rational Approaches to the Treatment oi Leukemia Moloney, W. c., Rosenthai, D. S.: Treatment of Early Acute Nonlymphatic Leukemia with Low Dose Cytosine Arabinoside.. 59 Rohatiner, A., Balkwill, F., Malpas, J.S., Lister, T. A.: A Phase I Study of Human Lymphoblastoid Interferon in Patients with Hematological Malignancies VII

6 Mertelsmann, R., Moore, M. A. S., Clarkson, B.: Methods and Clinical Relevance of Terminal Deoxynuc1eotidyl Transferase Determination in Leukemie Cells Hiddemann, W., Andreeff, M., Clarkson, B. D.: Quantitation of Chemotherapy-Induced Cytoreduction in Acute Leukemia Miller, D. R., Leikin, S., Albo, V., Sather, H., Karon, M., Hammond, D.: Intensive Therapy and Prognostic Factors in Acute Lymphoblastic Leuk~mia of Childhood: CCG 141. AReport from Childrens Cancer Study G roup Henze, G., Langermann, H.-J., Ritter, J., Schellong, G., Riehm, H.: Treatment Strategy for Different Risk Groups in Childhood Acute Lymphoblastie Leukemia: AReport From the BFM Study G roup Rivera, G.: Recurrent Childhood Lymphocytie Leukemia: Outcome of Marrow Relapses After Cessation of Therapy Sinks, L. F., Wang, J. J., Freeman, A. 1.: TheTreatmentofPrimary Childhood Acute Lymphocytic Leukemia with Intermediate Dose Methotrexate Chessells, J. M., Ninane, J., Tiedemann, K.: Present Problems in Management of Childhood Lymphoblastie Leukaemia: Experience from the Hospital for Siek Children, London Zintl, F., Plenert, W., Hermann, J.: Different Therapy Protocols for High Risk and Standard Risk ALLin Childhood Sallan, S. E.: T -Cell Acute Lymphoblastic Leukemia in Children Rodt, H., Thierfelder, S., Kolb, H. J., NetzeI, B., Haas, R J., Wilms, K., Bender-Götze, C.: The Concept of GvHD-Suppression by In Vitro Treatment with Antisera Storb, R.: Bone Marrow Transplantation for the Treatment of Leukemia Morgenstern, G. R, Powles, R L.: Allogeneic Bone Marrow Transplantation for Acute Myeloid Leukemia in First Remission Furusawa, M., Iino, T.: Use of Erythrocyte Ghosts fortherapy Hardesty, B., Henderson, A. B., Kramer, G.: A Possible Biochemieal Basis for the Use of Hyperthermia in the Treatment of Cancer and Virus Infection Cytogenetic Aspects of Lymphomas Rowley, J. D.: The Implications of Nonrandom Chromosome Changes for Malignant Transformation VIII

7 Carrano, A. v., Lebo, R V., Yu, L. c., Kan, Y. W.: Regional Gene Mapping of Human Chromosomes Purified by Flow Sorting Levan, G., Mitelman, F.: The Different Origin of Primary and Secondary Chromosome Aberrations in Cancer Cline, M. J., Stang, H. D., Mercola, K, Salser, W.: Insertion of NewGenesintoBoneMarrowCellsofMiee Scheer, D. 1., Srimatkandada, S., Kamen, B. A., Dube, S., Bertino, J. R: Organization of the Methotrexate Resistant Mouse L5178YR Dihydrofolate Reductase Gene and Transformation of HumanHCT-8CellsbyThisGene Hauser, H., Graf, T., Beug, H., Greiser-Wilke, 1., Lindenmaier, W., Grez, M., Land, H., Giesecke, K, Schütz, G.: Structure of the Lysozyme Gene and Expression in the Oviduct and Macrophages Zeuthen, J., Klein, G.: Some Recent Trends in Studies of Human Lymphoid Cells: B-Cells, Epstein-Barr Virus, and Transformation Wolf, H., Wilmes, E., Bayliss, G. J.: Epstein-BarrVirus: Its Siteof Persistence and Its Role in the Development of Carcinomas Kaschka-Dierich, c., Bauer, 1., Fleckenstein, B., Desrosiers, R C.: Episomal and Nonepisomal Herpesvirus DNA in Lymphoid Tumor Cell Lines Brade, L., Gissmann, L., Mueller-Lantzsch, N., zur Hausen, H.: B-Lymphotropic Papovavirus (LPV) - Infections of Man? Purtilo, D. T.: Immunopathology of the X-Linked Lymphoproliferative Syndrome Nilsson, K., Forsbeck, K., Gidlund, M., Sundström, c., Tötterman, T., SälIström, J., Venge, P.: Surface Characteristies of the U-937 Human Histiocytic Lymphoma Cell Line: Specific Changes During Inducible Morphologie and Functional Differentiation In Vitro Radzun, H. J., Parwaresch, M. R., Lennert, K: Enzyme Polymorphism as a Biochemical Cell Marker: Application to the Cellular Origin and Homogeneity of Human Macrophages and to the Classification of Malignant Lymphomas Wielckens, K, Garbrecht, M., Schwoch, G.,Hilz, H.: Human Leukemie Lymphocytes - Biochemical Parameters of the Altered Differentiation Status Diehl, V., Kirchner, H. H., Schaadt, M., Fonatsch, c., Stein, H.: Lymphoproliferation and Heterotransplantation in Nude Miee: Tumor Cells in Hodgkin's Disease IX

8 Cell Biological and Immunological Aspects Moore, Mo Ao So: Geneticand Oncogenic Influences on Myelopoiesis Broxmeyer, Ho Eo, Bognacki, Jo, Dörner, Mo Ho, desousa, Mo, Lu, L.: Acidic Isoferritins as Feedback Regulators in Normal and Leukemic Myelopoiesis Messner, Ho Ao, Fauser, Ao Ao, Buick, Ro, Chang, L. Jo-Ao, Lepine, Jo, Curtis, Jo Co, Senn, Jo, McCulloch, Eo A.: Assessment of Human Pluripotent Hemopoietic Progenitors and Leukemic Blast-Forming Cells in Culture Afanasiev, B. Vo, Elstner, Eo, Saidali, Mo Ao, Zabelina, To So: Proliferation and Maturation of Hemopoietic Cells in Adult Patients with Different Forms of Acute Leukemia and Chronic M yeloid Leukemia in Agar and Liquid Cultures Burk, Eo, Chennaoui-Antonio, L., Beiersdorf, Ho, Hellwege, Ho Ho, Winkler, Ko, Heinisch, Bo,Küstermann, Go, Krause, Uo, Kitschke, Ho Jo, Voigt, Ho, Neth, R.: Cytological and Cytochemical Analysis of Plasma Clot Cultures and Peripheral Granulocytes Related to Long Term Survival in Childhood ALL and Cancer Patients UnderCytostatica Therapy Hoelzer, Do, Harriss, Eo Bo, Carbonell, Fo: Maturation of Blast Cells in Acute Transformation of Chronic Myeloproliferative Syndrome Lau, B., Jäger, Go, Thiel, Eo, Pachmann, K., Rodt, Ho, Thierfelder, So, Dörmer, Po: Patterns of Cell Surface Differentiation of call Positive Leukemic Blast Cells in Diffusion Chamber Culture Forbes, Po, Dobbie, Do, Powles, Ro, Alexander, Po: Maturation of Human Peripheral Blood Leukemic Cells in Short-Term Culture Dexter, To Mo: Regulator-Dependent Hemopoiesis and Hs Possible Relevance to Leukemogenesis Gartner, So, Kaplan, Ho So: Long-Term Culture of Normal and LeukemicHumanBoneMarrow Greenberg, Ho Mo, Parker, L. Mo, Newburger, Po Eo, Said, Jo, Cohen, Go 1., Greenberger, Jo So: Corticosteroid Dependence of Continuous Hemopoiesis In Vitro with Murine or Human Bone Marrow Mitchison, No A.: Cloning Cells ofthe Immune System Greaves, Mo Fo, Robinson, Jo Bo, Delia, Do, Ritz, Jo, Schlossman, So, Sieff, Co, Goldstein, Go, Kung, Po, Bollum, Fo J 0' Edwards, Po A. Wo: Comparative Antigenic Phenotypes of Normal and Leukemic Hemopoietic Precursor Cells Analysed with a "Library" of Monoclonal Antibodies x

9 van den Engh, G., Trask, B., Visser, J.: Surface Antigens of Pluripotent and Committed Haemopoietic Stern Cells BeverIey, P. C. L., Linch, D., Callard, R. E.: Human Leucocyte Antigens Godal, T., Lindrno, T., Ruud, E., Heikkilä, R., Henriksen, A., Steen, H. B., Marton, P. F.: Immunologic Subsets in Human B-Cell Lymphomas in Relation to Normal B-Cell Development Hengartner, H.: Clones ofmurine Functional TCells Minowada, J.: Marker Profiles of Leukemia-Lymphoma Cell Lines Newman, R. A., Sutherland, D. R., Greaves, M. F.: Biochemical Characterization of an Antigen Associated with Acute Lymphoblastic Leukemia and Lymphocyte Precursors Becker, W.-M., Schmiegel, W.-H., Kabisch, H., Arndt, R., Thiele, H.-G.: SerologicSubtypingofcALL Baker, M. A., Roncari, D. A. K., Taub, R. N., Mohanakumar, T., Falk, J. A.: Acute Myeloblastic Leukemia-Associated Antigens: Detection and Clinicallmportance Andersson, L. c., von Willebrand, E., Jokinen, M., Karhi, K. K., Gahmberg, C. G.: Glycophorin A as an Erythroid Marker in Normal and Malignant Hematopoiesis Eichmann, K.: The Network Concept and Leukemia Klein, E.: Interpretation and In Vivo Relevance of Lymphocytotoxicity Assays Milleck, J., Jantscheff, P., Thränhardt, H., Schöntube, M., Gürtler, R., Seifart, D., Pasternak, G.: Acute Leukemia, and Nonspecific Killer Cells Teodorescu, M., Hsu, C., Bratescu, A., DeBoer, K. P., Nelson, R., Kleinman, R., Wen, C. M.-J., Mayer, E. P., Pang, E. J.-M.: The Use of Bacteria as Markers of Leukemic Lymphocytes and for the Isolation of Natural Killer Cells... _' McGrath, M. S., Jerabek, L., Pillemer, E., Steinberg, R. A., Weissman, I. L.: Receptor Mediated Murine Leukemogenesis: Monoclonal Antibody Induced Lymphoma Cell Growth Arrest 360 Stoye, J. P., Moroni, c.: Effect of Brombdeoxyuridine on Endogenous Retrovirus Production in Differentiating Murine Lymphocytes Schreiber, H., Flood, P. M., Kripke, M. L., Urban, J. L.: Modulation of Growth of Malignant Cells by Anti-Idiotypic Immunity XI

10 Kyewski, B., Hunsmann, Go, Friedrich, R., Ketelsen, Uo-Po, Wekerle, Ho: Thymic Nurse Cells: Intraepithelial Thymocyte Sojourn and Its Possible Relevance for the Pathogenesis of AKR Lymphomas Schirrmacher, Vo, Bosslet, Ko: Generation of Stable Antigen Loss Variants from Cloned Tumor Lines - An Example of Immunoadaptation During Metastasis Virological and Molecularbiological Aspects Duesberg, Po Ho, Bister, Ko: Transforrning Genes of Retroviruses: Definition, Specificity, and Relation to Cellular DNA Erikson, Eo, Erikson, R. L. : A Cellular Protein Phosphorylated by the Avian Sarcoma Virus Transforming Gene Product Friis, R. R., Ziemiecki, Ao, Bosch, Vo, Boschek, C. Bo, Bauer, Ho: Correlated Loss of the Transformed Phenotype and pp60src-associated Protein Kinase Activity Moelling, K., Owada, Mo K., Donner, Po, Bunte, To: The Transformation-Specific Protein pp60src from an A vian Sarcoma Virus Konze-Thomas, Bo, von der Helm, K.: Proteolytic Processing of Avian and Simian Sarcoma and Leukemia Viral Proteins Kramer, Go, Grankowski, No, Hardesty, Bo: Control of Protein Synthesiso Phosphorylation and Dephosphorylation of Eukaryotic Peptide Initiation Factor Graf, To, Royer-Pokora, Bo, Korzeniewska, Eo, Grieser, So, Beug, Ho: Characterization of the Hematopoietic Target Cells of Defective Avian Leukemia Viruses by Velocity Sedimentation and Density Gradient Centrifugation Analyses Vogt, Po K., Neil, Jo c., Moscovici, c., Breitman, Mo L.: PRCII, a Representative of a New Class of Avian Sarcoma Virus es Souza, L. Mo, Bergmann, Do Go, Baluda, Mo Ao: Identification of theavianmyeloblastosisvirusgenome Coffin, Jo Mo, Tsichlis, Po No, Robinson, Ho L.: Genetics of Leukemogenesis by Avian Leukosis Viruses Hayward, Wo So, Neel, B. Go, Fang, Jo, Robinson, Ho L., Astrin, So Mo: Avian Lymphoid Leukosis is Correlated with the Appearance of Discrete New RNAs Containing Viral and Cellular Genetic Information Kung, Ho Jo, Fung, Yo K., Crittenden, L. Co, Fadly, A., Dube, So K.: The Molecular Basis of Avian Retrovirus-Induced Leukemogenesis XII

11 Löliger, Ho-C., von dem Hagen, Do, Hartmann, Wo: Studies of the Association of Leukemogenic and Oncogenic Properties in Avian Leukemia Viruses Aaronson, So Ao, Barbacid, Mo, Dunn, C. Yo, Reddy, Eo Po: Genetic Approaches Toward Elucidating the Mechanisms of Type-C Virus-InducedLeukemia Blair, Do Go, Oskarsson, Mo, McClements, Wo L., Vande Woude, Go Fo: The Long Terminal Repeat of Moloney Sarcoma Provirus Enhances Transformation Waneck, Go L., Rosenberg, No: Ontogeny of Abelson Murine Leukemia Virus Target Cells Evans, L. Ho, Duesberg, Po Ho, Linemeyer, Do L., Ruscetti, So Ko, Scolnick, Eo Mo: Structural and Functional Studies of the Friend Spleen Focus-Forming Virus: Structural Relationship of SFFV to Dualtropic Viruses and Molecular Cloning of a Biologically Active SubgenomicFragmentofSFFVDNA van den Berg, Ko Jo, Krump-Konvalinkova, Vo, Bentvelzen, Po: Enhancing Effect of Murine Leukemia Virus on Fibroblast Transformation by Normal BALB/C Mouse DNA Fragments Essex, Mo, Grant, Co K., Cotter, So Mo, Hardy, Wo Do Jr.: Role of Viruses in the Etiology of Naturally Occuring Feline Leukemia Snyder, Ho Wo Jr., Dutta-Choudhury, Mo, Hardy, Wo Do Jr.: Relationship of the Feline Oncornavirus Associated Cell Membrane Antigen to a Feline Sarcoma Virus Encoded Polyprotein Hardy, Wo Do Jr., McClelland, Ao Jo, Zuckerman, Eo Eo, Snyder, Ho Wo Jr., MacEwen, Eo Go, Francis, Do, Essex, Mo: Feline Leukemia Virus Nonproducer Lymphosarcomas of Cats as a Model for the EtiologyofHumanLeukemias Kettmann, Ro, Marbaix, Go, Mammerickx, Mo, Burny, Ao: Genomic Integration of Bovine Leukemia Provirus and Lack of Viral RNA Expression in the Target Cells of Cattle with Different Responses to BLV Infection Portetelle, Do, Bruck, c., Mammerickx, Mo, Burny, Ao: Natural Antibodies to BLV gp51 Are Reactive Against the Carbohydrate Moiety ofthe Glycoprotein Gallo, R. c., Poiesz, B. Jo, Ruscetti, F. Wo: Regulation of Human T -Cell Proliferation: T -Cell Growth Factor and Isolation of a New Class of Type-C Retroviruses from Human T -Cells Reitz, Mo So Jr., Poiesz, B. Jo, Ruscetti, Eo Wo, Gallo, R. Co: Characterization by Nucleic Acid Hybridization of HTLV, a Novel Retrovirus from Human Neoplastic T -Lymphocytes XIII

12 Torelli, U., Torelli, G., Narni, F., Donelli, A., Ferrari, S., Franchini, G., Calabretta, B.: Different Frequency Classes of Sequences in Heterogeneous Nuc1ear RNA of Normal Promyelocytes and Lymphoblasts and of Leukemic Blast Cells of Circulating Blood and of the HL60 Line Thiel, H.-J., Matthews, T., Broughton, E., Butchko, A., Bolognesi, D.: Characterization of Antigens in SSV Nonproducer Cells Bergholz, C. M.: Viral Gene Expression in Cells Transformed by Simian Sarcoma Virus, an Infectious Primate Type C Retrovirus Jore, J., Dubbes, R., Coolen, J., Nooter, K.: Cell Fusion as a Tool for the Detection of Viral Footprints in Childhood Leukemia Hehlmann, R., Schetters, H., Erfle, V.: ELISA for the Detection of Antigens Cross-Reacting with Primate C-Type Viral Proteins (p30, gp70) in Human Leukemic Sera Erfle, V., Hehlmann, R., Schetters, H., Schmidt, J., Luz, A.: Radiation-Induced Murine Leukemias and Endogenous Retroviruses: The Time Course of Viral Expression Löwer, J., Löwer, R., Stegmann, J., Frank, H., Kurth, R.: Retrovirus Partic1e Production in Three of Four Human TeratocarcinomaCeliLines., General Summary Deinhardt, F.: General Summary 547 Subject Index Speciallecture far the Wilsede Joint Meeting on Pediatric Oncology I 2 Were also presented in the Wilsede Joint Meeting on Pediatric Oncology I XIV

13 Participants of the Meeting Aaronson, A., Laboratory of RNA Tumor Viruses, National Cancer Institute, Bethesda, MD 20014, USA Andersson, L., Transplantation Laboratory, University of Helsinki, Haartmaninkatu 3A, Helsinki 29, Finland Andreeff, M., Memorial Sloan-Kettering Cancer Center, 1275 Y ork Avenue, New York, NY 10021, USA Baluda, M. A., UCLA Cancer Center, Dept. Microbiology and Immunolgy, 921 Westwood Boulevard, Los Angeles, CA 90024, USA Barbacid, M., Laboratory of RNA Tumor Viruses, National Cancer Institute, Bethesda, MD 20014, USA Beck, J. D., Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA Bentvelzen, P., Radiobiological Institute, 151 Lange Kleiweg, Rijswijk, The Netherlands Bertino, J., Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA Beverley, P. C. L., ICRF Human Tumour Immunology Group, University of London, University Street, London WC1E6JJ, U.K. Bister, K., Dept. Molecular Biology, Wendel! M. Stanley Hall, University of Califomia, Berkeley, CA 94720, USA Brade, Lore, Institut für Virologie im Zentrum für Hygiene, Hermann-Herder Straße 11,7800 Freiburg i. Br., West-Germany Bumy, A., Faculte des Sciences Agronomiques de l'etat, Chaire de Zootechnie, Gembloux, Belgium ' Carrano, A., Biomedical Division, L-452, Lawrence Livermore Labs. Livermore, CA 94550, USA Chermann, J.-C., Institut Pasteur, 25, Rue du Docteur Roux, Paris, Cedex 15, France Cline, M., UCLA Center for Health Sciences, Dept. Medicine, Los Angeles, CA 90024, USA Coffin, J. M., Dept. Molecular Biology, Tufts University, 1.36 Harrisbn Avenue, Boston, MA 02111, USA Deinhardt, F., Max v. Pettenkofer-Institut, Pettenkoferstraße 9a, 8000 München 2, West-Germany Dexter, T. M., Christie Hospital & Holt Radium Institute, Paterson Laboratories, Manchester M20 9BX, U.K. Diehl, V., Medizinische Hochschule Hannover, Depärtment für Innere Medizin, Karl-Wiechert-Allee 9, 3000 Hannover-Kleefeld, West-Germany Duesberg, P., Dept. Molecular Biology, Wendel! M. Stanley HaI!, University of Califomia, Berkeley, CA 94720, USA Eichmann, K., Krebsforschungszentrum - Immunologie, Im Neuenheimer Feld 280, 6900 Heidelberg, West-Germany Elstner, Elena, Abt. Zellkinetik, Zentralinstitut für Molekularbiologie, Lindenberger Weg 70, 1115 Berlin-Buch, GDR xv

14 van den Engh, G., Radiobiological Institute 151 Lange Kleiweg, Rijswijk, The Netherlands Erfle, V., Gesellschaft für Strahlen- und Umweltschäden, Ingolstädter Landstraße 1,8042 Neuherberg, West-Germany Erikson, Eleanor, Health Sciences Center, University of Colorado, 4200 East Ninth Avenue, Denver, CO 80262, USA Essex, M., Dept. Microbiology, Harvard School of PubIic Health, 665 Huntington Avenue, Boston, MA 02115, USA Evans, L., Dept. Molecular Biology, WendelI M. Stanley Hall, University of CaIifomia, Berkeley, CA 92720, USA Feldman, M., The Weizmann Institute of Science, P.O. Box 26, Rehovot , Israel Fleckenstein, B., Institut für Klinische Virologie, Loschgestraße 7,8520 Erlangen, West-Germany Forbes, Penelope, Chester Beatty Research Institute, CIifton Avenue, Belmont, Sutton, Surrey SM2 5PX, U.K. Frei IH, E., Sidney Farber Cancer Institute, 44, Binney Street, Boston, MA 02115, USA Friis, R. R., Institut für Virologie, Justus-Liebig-Universität, Frankfurter Straße 107,6300 Gießen, West-Germany Furusawa, M., Dept. Biology, Osaka City University, Sugimoto-Cho, Surniyoshi Ku, Osaka 558, Japan Gallo, R. c., National Cancer Institute, Bethesda, MD 20014, USA Gartner, Suzanne, Dept. Radiology, Cancer Biology Research Laboratory, Stanford University Medical Center, Stanford, CA 94305, USA Georgii, A., Medizinische Hochschule Hannover, Pathologisches Institut, Karl Wichert-Allee 9, 3000 Hannover-Kleefeld, West-Germany Godal, T., Norsk Hydro's Institute for Cancer Research, Montebello, Oslo 3, Norway Graf, T., Institut für Virusforschung, Im Neuenheimer Feld 280, 6900 Heidelberg 1, West-Germany Greaves, M. F., Imperial Cancer Research Fund Laboratories, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, U.K. Greenberger, J. S., Dept. Radiation Therapy, Harvard Medical School, 44, Binney Street, Boston, MA 02115, USA Hardesty, B., Dept. Chemistry, The Clayton Foundation Biochemical Institute, University of Texas, Austin, TX 78712, USA Hausen, H. zur, Institut für Virologie im Zentrum für Hygiene, Hermann-Herder Straße 11, 7800 Freiburg i. Br., West-Germany Hayward, W., Rockefeller University, 1230 York Avenue, NewYork, NY 10021, USA Hehlmann, R., Institut für Biologie, Ingolstädter Landstraße 1,8042 Neuherberg, West-Germany Helm, K. von der, Max v. Pettenkofer-Institut, Pettenkoferstraße 9a, 8000 München 2, West-Germany Hengartner, H., Experimentelle Pathologie, Universität Zürich, Schmelzbergstraße 12, 8091 Zürich, Switzerland Hölzer, D., Zentrum für Innere Medizin und Kinderheilkunde, Universität lilm, Steinhövelstraße 9, 7900 Ulm, West-Germany Kabisch, H., Universitäts-KinderkIinik, Abt. für Hämatologie und Onkologie, Martinistr. 52, 2000 Hamburg 20, West-Germany Kaplan, H. S., Dept. Radiology, Cancer Biology Research Laboratory, Stanford University Medical School, Stanford, CA 94305, USA Kettmann, R., Faculte des Sciences Agronomiques de l'etat, Chaire de Zootechnie, Gembloux, Belgium Klein, Eva, Dept.Tumor Biology, KaroIinska Institutet, 104 Stockholm 60, Sweden Klein, G., Dept. Tumor Biology, KaroIinska Institutet, 104 Stockholm 60, Sweden Kirsten, W. H., Dept. Pathology, University of Chicago, 950 East 50th Street, Chicago, IL 60637, USA Kramer, Gisela, Dept. Chernistry, The CIayton Foundation Biochernical Institute, University of Texas, Austin, TX 78712, USA XVI

15 Kurth, R., Friedrich-Miescher-Laboratorium der Max-Planck-Gesellschaft, Spemannstraße 37-39, 7400 Tübingen, West-Germany Lajtha, L. G., Christie Hospital & Holt Radium Institute, Paterson Laboratories, Manchester M20 9BX, U.K. Lau, Barbara, Gesellschaft für Strahlen- und Umweltforschung mbh, Abteilung Experimentelle Hämatologie und Immunologie, Landwehrstraße 61, 8000 München 15, West-Germany Levan, G., Genetiska Institutionen, Göteborgs Universitet, Stigbergsliden 14, Göteborg, Sweden Linemeyer, D. L., National Cancer Institute, Bethesda, l'vid 20014, USA Lister, A., Dept. Medical Oncology, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, U.K. Löliger, H.-Ch., Institut für Kleintierzucht, Dörnbergstraße 25-27, 3100 Celle, West-Germany Mannweiler, K., Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Martinistraße 52, 2000 Hamburg 20, West-Germany Mayer, R., Sidney Farber Cancer Institute, 44, Binney Street, Boston, MA 02115, USA McCredie, K. B., Leukemia Service, M. D. Anderson Hospital, 6723 Bertner Avenue, Houston, TX 77030, USA McGrath, M., Dep!. Pathology, Stanford University Medical Center, Stanford, CA 94305, USA Mercola, Karen, Dept. Medicine, University of California, Los Angeles, CA 90024, USA Mertelsmann, R., Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA Messner, H., The Ontario Cancer Institute, 5000 Sherbourne Street, Toronto, Ontario M4X, 1K9, Canada Milleck, J., Zentralinstitut für Krebsforschung, Lindenbergerweg 80,115 Berlin Buch, GDR Miller, D. R., Memorial Sloan-Kettering Cancer Center, 1275 YorkAvenue, New York, NY 10021, USA Minowada, J., Roswell Park Memorial Institute, 666 Elm Street, Buffalo, NY 14263, USA Mitchison, N. A., Tumor Immunolgy Unit, University College London, Gower Street, London WC1E 6BT, U.K. Mölling, Karin, Max-Planck-Institut für Molekulare Genetik, Ihnestraße 63-73, 1000 Berlin 33, West-Germany Moloney, W. c., Peter Bent Brigham Hospital. Hematology Division, 721 Huntington Avenue, Boston, MA 02115, USA Moore, M. A. S., Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA Munk, K., Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 6900 Heidelberg, West-Germany Neth, R., Universitäts-Kinderklinik Hamburg-Eppendorf, Martinistraße 52, 2000 Hamburg 20, West-Germany Newman, R., Imperial Cancer Research Fund Laboratories, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, U.K. Nilsson, K., The Wallenberg Laboratory, Box 562, University of Uppsala, Uppsala, Sweden Nooter, K., Radiobiological Institute, 151 Lange Kleiweg, Rijswijk, The Netherlands Pragnell, 1., Beaton Institute for Cancer Research, Switchback Road, Bearsden, Glasgow G61 IBD, Scotland Preisler, H., Roswell Park Memorial Institute, 666 Elm Street, Buffalo, NY 14263, USA Purtilo, D. T., Dept. Pathology, University of Massachusetts Medical Center, Worcester, MA 01605, USA Radzun, H. J., Klinikum der Christian-Albrechts-Universität Kiel, Institut für Pathologie, Hospitalstraße 42, 2300 Kiel, West-Germany XVII

16 Reitz, M., National Cancer Institute, Bethesda, MD 20014, USA Riehm, H. J., Kinderklinik der Freien Universität Berlin, Heubnerweg 6, 1000 Berlin 19, West-Germany Rivera, G., St. Jude Children's Research Hospital, 332 North Lauderdale, P.O. Box 318, Memphis, TN 38101, USA Rodt, H., Institut für Hämatologie, Abteilung Immunologie, Landwehrstraße 61, 8000 München 2, West-Germany Rohatiner, A., Dept. Medical Oncology, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, U.K. Rosenberg, Naomi E., Cancer Research Center, Tufts University School of Medicine, 136 Huntington Avenue, Boston, MA 02111, USA Rowley, Janet D., Dept. Medicine, Section of Hematology/Oncology, Box 420, 950 East 59th Street, Chicago, IL 60637, USA Sallan, S. E., Sidney Farber Cancer Institute, 44, Binney Street, Boston, MA 02115, USA Scherrer, K., Institut de Recherche Biologie-Moleculaire, F Paris Cedex 5, France Schirrmacher, V., Institut für Virusforschung, Im Neuenheimer Feld 280, 6900 Heidelberg 1, West-Germany Schreiber, H., Dept. Pathology, La Rabida Children's Hospital and Research Center, East 65th Street at Lake Michigan, Chicago, IL 60649, USA Simon, M. M., Krebsforschungszentrum - Immunologie, Im Neuenheimer Feld 280, 6900 Heidelberg, West-Germany Stegmann, J., Friedrich-Miescher-Laboratorium der Max-Planck-Gesellschaft, Spemannstraße 37-39, 7400 Tübingen 1, West-Germany Stehelin, D., Institut Pasteur de Lilie, 15 rue Camille Guerin, B. P. 3415, Lilie, France Storb, R., Division of Oncology, Providence Hospital, th Avenue, Seattle, WA 98122, USA Stoye, J., Friedrich-Miescher-Institut, Grenzacherstraße 487, 4002 Basel, Switzerland Stuhlmann, Heidi, Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Martinistraße 52, 2000 Hamburg 20, West-Germany Teich, Natalie M., Imperial Cancer Research Fund Laboratories, Lincoln's Inn Fields, London WC2A 3PX, U.K. Teodorescu, M., Dept. Microbiology, Medical Center, University of Illinois, Chicago, IL 60612, USA Thiel, J., Medical Center, Dept. Surgery, Duke University, Durham, NC 27710, USA Torelli, U., Instituto di Patologia Speciale Medica e Metodologia Clinica, Via dei Pozzo, 71, Modena, Italy Van de Woude, G., National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20014, USA Vogt, P. K., Dept. Microbiology, USC Medical Center, 2025 Zonal Avenue, Los Angeles, CA 90034, USA Wernet, P., Medizinische Klinik, Abteilung Innere Medizin, Otfried-Müller-Straße, 7400 Tübingen, West-Germany " Wielckens, K., Physiologisch-Chemisches Institut, Martinistraße 52, 2000 Hamburg 20, West-Germany Wekerle, H., Max-Planck-Institut für Immunbiologie, Stübeweg 51, 7800 Freiburg-Zähringen, West-Germany Witz, 1. P., Faculty of Life Science, Dept. Microbiology, Tel-Aviv University, Tel Aviv, Israel Wolf, H., Max v. Pettenkofer-Institut, Pettenkoferstraße 9a, 8000 München 2, West-Germany Yohn, D. S., OSU Comprehensive Cancer Center, McCampbell Hall, Columbus, OH4310, USA Zeuthen, J., Institute for Human Genetics, Bartholin Byggningen, Aarhus University, 8000 Aarhus C, Denmark Zintl, F., Universitäts-Kinderklinik, Kochstraße 2, 69 Jena, GDR XVIII

17 Wilsede Scholarship Holders (Granted by the Deutsche Krebshilfe and the Leukemia Society of America) Andreesen, Reinhard, Medizinische Univ.-Klinik, Hugstetter Straße 55, D-7800 Freiburg Bamekow, Angelika, Institut für Virologie der Justus-Liebig Universität Gießen, Fachbereich Humanmedizin, Frankfurter Straße 107, D-6300 Gießen Bergholz, Carolyn, Dept. Microbiology, Medical Sciences Building, University of Illinois, Urbana, IL 61801, USA Berhold, Rosemarie, Univ.-Kinderpoliklinik Gießen, Feulgenstraße 12, D-6300 Gießen Breu, Herbert, Kinderklinik der Westfälischen Wilhelms-Universität, Abteilung für Hämatologie und Onkologie, Robert-Koch-Str. 31, D-4400 Münster Broxmeyer, HaI. E., Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA Carbonell, Felix, Abt. für klinische Physiologie, Universität Ulm, Oberer Eselsberg, D-7900 Ulm Dölken, Gottfried, Klinikum der Albert-Ludwigs-Universität, Med. Univ.-Klinik, Hugstetter Straße 55, D-7800 Freiburg Dube, Shyam, Dept. Epiderniology, Yale University, 60 College Street, New Haven, er 06510, USA Freudenstein, Christa, Deutsches Krebsforschungszentrum - Institut für Virusforschung, Im Neuenheimer Feld 280, D-6900 Heidelberg Gaedicke, Gerhard, Zentrum für Kinderheilkunde, Abt. Hämatologie II, Prittwitzstr. 43, D-7900 Ulm Hagner, Gerhard, Freie Universität Berlin, Universitätsklinikum Charlottenburg, Abt. Innere Medizin m.s. Hämatologie und On:kologie, Spandauer Damm 130, D-1000 Berlin 19 Harbers, Klaus, Heinrich-Pette-Institut für Experimentelle Viorologie und Immunologie an der Universität Hamburg, Martinistr. 52, D-2000 Hamburg 20 Hardy, William Jr., Memorial Sloan-Kettering Cancer Center, Laboratory of Veterinary Oncology, 1275 York Avenue, New York, NY 10021,. USA Henze, Günter, Universitätskinderklinik, Heubnerweg 6, D B~rlin 19 Heilbronn, Regine, Stadtstraße 4, D-7800 Freiburg IsseIs, Rudolf, Ludwig-Maxirnilians-Universität München, Klinikum Großhadern, Med. Klinik III, Marchionistr. 15, D-8000 München 70 Janka, Gritta, Abt. f. Hämatologie und Onkologie, Kinderklinik der Universität München im Dr. von Haunerschen, Kinderspital, Lindwurmstr. 4, D-8000 München Koeppen, Klaus-Michael, Krankenhaus Neukölln, II. Innere Abteilung, Rudower Str. 56, D-1000 Berlin 47 Konze-Thomas, Beate, Max v. Pettenkofer-Institut für Hygiene und Med. Mikrobiologie der Ludwig-Maxirnilians-Universität, Pettenkoferstr. 9a, D-8000 München 2 Meier, Claus Richard, Gesellschaft für Strahlen- und Umweltforschung mbh, Landwehrstr. 61, D-8000 München XIX

18 Meyer, Peter, Eberhard-Karls-Universität, Abt. Innere Med. 11, Otfried-Müller- Str. 25, D-7400 Tübingen Müller, Stephan, Universitätskinderklinik, Heubnerweg 6, D-I000 Berlin 19 Nerl, Christoph, Straßberger Str. 20, D-8000 München 40 Ritter, Jörg, Universitäts-Kinderklinik, Abt. für Hämatologie und Onkologie und der Poliklinik, Robert-Koch-Str. 31, D-4400 Münster Schmitz, N., Zentrum für Innere Medizin am Klinikum der Justus-Liebig-Universität, D-6300 Gießen Seelis, Rudolfo E. A., Abt. Innere Medizin 11 der Med. Fakultät an der Rhein-Westf.-Techn. Hochschule Aachen, Goethestr , D-5100 Aachen Siegert, Wolfgang, Med. Klinik 111, Klinikum Großhadern, Marchionistr. 15, D-8000 München Snyder, Harry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA Stünkel, Klaus, Gesellschaft für Strahlen- und Umweltforschung mbh, Landwehrstr. 61, D-8000 München Wernicke, Dorothee, Friedrich-Miescher-Laboratorium der Max-Planck-Gesellschaft, Spemannstr , D-7400 Tübingen Weh, Hans-Josef, Akazienstr. 13, D-6501 Klein-Winternheim Ziegler, Andreas, Med. Klinik, Innere Abteilung, Eberhard-Karls-Universität, Otfried-Müller-Str., D-7400 Tübingen xx

19 Preface Gut ist eine Lehrart, wo man vom Bekannten zum Unbekannten fortschreitet; schön ist sie, wenn sie sokratisch ist, d.i. wenn sie dieselben Wahrheiten aus dem Kopf und Herzen des Zuhörers herausfragt. Bei der ersten werden dem Verstand seine Uberzeugungen in Form abgefordert, bei der zweiten sie ihm abgelockt. Professor Friederich Schiller Jena, in a letter written on 23 February 1793 to his friend and supporter Körner, father of the poet Theodor Körner. Established clinicians and scientists as weil as students aga in tried the Wilsede experiment for three days and nights and learned from each other. In our fourth Wilsede meeting on "Modern Trends in Human Leukemia" we concentrated once again on questions re gar ding the practical application of research and its benefits to the patient. The main emphasis of leukemia research has changed since the first Wilsede meeting in Virology is no longer the sole interest. Advances in immunology and cell genetics and a better understanding of Dr. h. c. Alfred Toepfer speeking with participants of the meeting in Wilsede XXI

20 Arrival and discussion of participants in front of the meeting pi ace " De Emmenhoff" XXII

21 Personal and scientific discussion in Wilsede June 1980 Fotos: R. Völs XXIII

22 the mechanisms regulating normal and pathological blood cell differentiation have had a considerable impact on the direction of leukemia research. I would like to thank all chairmen for their efforts in organizing a program which included most of the important results and also future aspects of human leukemia. We have learned at the Wilsede meeting that the individual fields of interest raise similar cell biological questions, the solution of which require increasing efforts for multidisciplinary collaboration. At the next Wilsede meeting in 1982 new insights certainly will have become apparent through additional knowledge in the field of cytogenetics of cancer cells and through new possibilities in the application of monoc1onal antibodies and purification of specific regulatory proteins with inhibitory and stimulating effects on blood cell differentiation. During the meeting we usually stayed in De Emmenhoff in Wilsede. We would like to express our gratitude to all Wilsede people for their hospitality and also to the Verein Naturschutzpark e.v., and last but not least to Dr. Alfred Toepfer and his associates for their idealistic efforts to preserve this peaceful place for uso Hamburg, April 1981 RolfNeth XXIV

23 Acknowledgement We should like to thank all who made this workshop possible: Deutsche Forschungsgemeinschaft* Deutsche Krebshilfe Deutsches Krebsforschungszentrum Heidelberg Freie und Hansestadt Hamburg Hamburger Landesverband für Krebsbekämpfung und Krebsforschung e.v. Hamburgische Wissenschaftliche Stiftung Internationale Union Against Cancer (UICC)** Leukemia Society of America Paul Martini Stiftung Niedersächsisches Sozialministerium Universität Hamburg (Hertha-Grober-Stiftung) For generous hospitality we thank the Stiftung F. V. S. zu Hamburg, the Amerikahaus in Hamburg, the Freie and Hansestadt Hamburg, the Hamburger Staatsoper and the HADAG Seetouristik und Fährdienst AG * Contract No. 4851/10/79 ** National Cancer Institute, National Institutes of Health, Contract No. N01-CO xxv