Molecular Biology of Hematopoiesis 5 Molecular Biology of Helllatopoiesis 5 Edited by Nader G. Abraham The Rockefeller University New York, New York Shigetaka Asano University of Tokyo Tokyo, Japan Gunther Brittinger Universitiit-Gesamthoschschule Essen Essen, Germany Georges J. M. Maestroni Istituto Cantonale di Patologia Locarno, Switzerland and Richard K. Shadduck Western Pennsylvania Cancer Institute Pittsburgh, Pennsylvania Plenum Press • New York and London L1brary of Congress Catalog1ng-1n-PubI1cat1on Data Molecular biology of hematopoiesis 5 I edited by Nader G. Abraham ... [eta1.l. p. cm. "Proceedings of the Ninth Symposium on the Molecular Biology of Hematopoiesis. held June 23-27, 1995, in Genoa, Italy"--T.p. verso. Inc 1u des bib 1 i ograph i ca 1 references and index. 1. Myeloproliferative disorders--Molecular aspects--Congresses. 2. Hematopoietic stem cell disorders--Molecular aspects--Congresses. 3. Hematopoiesis--Congresses. 4. Bone marrow--Transplantation- -Molecular aspects--Congresses. I. Abraham, Nader G. II. Symposium on the Molecular Biology of Hematopoiesis (9th 1995 Genoa, Italy) [DNLM: 1. Hematopoiesis--congresses. ~H 140 M7177 1996] RC645.75.M65 1996 616.4' 107--dc20 DNLM/DLC for Library of Congress 96-27564 CIP Proceedings of the Ninth Symposium on the Molecular Biology of Hematopoiesis, held June 23 -27,1995, in Genoa, Italy ISBN-13: 978-1-4613-8031-3 e-ISBN-13: 978-1-4613-0391-6 DOl: 10.1007/978-1-4613-0391-6 © 1996 Plenum Press, New York Softcover reprint of the hardcover I st edition 1996 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N. Y. 10013 All rights reserved 1098765432 I No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Volumes 1-4 were published by Intercept, Ltd., Andover, United Kingdom PREFACE This volume of Molecular Biology ofH ematopoiesis is dedicated to John W. Adam son, M.D., Tadamitsu Kishimoto, M.D., Robert C. Gallo, M.D., Arthur W. Nienhuis, M.D., and Franco Mandelli, M.D., for their contributions in developing an overall view of the state-of-the-art knowledge in the field of hematopoiesis. Richard Champlin, among other renowned clinicians, presented updated information on stem cells and T-cell depletion for bone marrow transplant. A clinical update on thrombopoietin was presented by Pamela Hunt of Amgen and by Kenneth Kaushansky. Arthur Nienhuis' and Katherine Turner's contribu tions to our current knowledge and advances in the fields of growth factors and gene transfer were also recognized during the 9th Symposium on Molecular Biology of Hematopoiesis in Genoa. The chapters cover such diverse areas as preclinical and clinical updates on growth factors and positive and negative regulatory molecules. "Advances in Leukemia: Mechanism and Treatment by Interferon" was presented by Professor Sante Tura. Readers will find presentation of exciting advances that have occurred in the area of hematopoiesis. The elucidation of gene structures of key growth factor proteins such as IL-12 and IL-II will lead to new insights and new approaches in understanding the regulation of hematopoiesis, as well as application of new growth factors. Retrovirus gene transfer techniques and genetic manipulation of murine and human cells have added new information on the regulatory steps involved in cell development and genetic disorders. Transfection of eukaryotic cells, specifically bone marrow cells and, subsequently, in vivo transplantation, further suggest that hematopoietic reconstitution is possible. Studies of gene transfer continue to reveal the mechanism behind various biological events in which normal and abnormal cell proliferation and differentiation will be achieved. Further, origination and isolation of stem cells, as well as the use of cord blood for bone marrow transplant, were presented. Enthusiasm for the discovery of new growth factor( s) and interleukin(s) remains strong as novel factors are introduced into the field and presented at the meeting. Also, exciting data are being generated in linking growth factors and neuroendocrines to proto-oncogenes and cell proliferation and differentiation. More data will continue to accrue, in particular, with respect to the cell surface receptors, the mecha nisms of shut-off of local production of these factors, and possible clinical side effects of their continued administration. We are convinced that this volume will be a useful reference for clinicians, scientists, and investigators who are interested in the field of hematopoiesis. Nader G. Abraham v ACKNOWLEDGMENTS The Organizing Committee wishes to acknowledge the Menarini International Foun- dation and the following companies, whose support made this meeting possible: • Amgen-Roche, SpA • Chugai Rhone-Poulenc • Ortho Biotech • CellPro Inc., Europe N.V'/S.A. • Schering Plough SpA • Wellcome Italia SpA • Glaxo Group Research Limited • Baxter Healthcare Corporation • Miltenyi Biotec • Schering Plough International • Blackwell Science • Le Petit (Marion-Merrell Dow) • Impress • Stem Cell • SyStemix • Ortho Biotech Inc. • Beckman • Sandoz • Immunokontact • Vestar • Liposome • Stockton • Pasteur Merieux • Fondaz. Int. Menarini .OPA • Intercept • Plenum The Organizing Committee gratefully acknowledges the patience and support, in cluding editorial assistance, in preparation of this conference of Joyce Eshet, Symposium Coordinator. vii viii Acknowledgments For further infonnation, please write to: N.G. Abraham New York University School of Medicine Brooklyn Hospital Campus Brooklyn, NY 11201 or The Rockefeller University 1230 York Avenue New York, NY 10021 EDITORS'/PUBLISHER'S DISCLAIMER Papers or parts thereof have been used as camera-ready copy as submitted by the authors whenever possible; when retyped. they have been edited by the editorial staff only to the extent considered necessary for the assistance of an international readership. The views expressed and the general style adopted remain. however. the responsibility of the named author. Great care has been taken to maintain the accuracy of the infonnation contained in the volume. However. neither the publisher nor the editors can be held responsible for errors or for any consequences arising from the use of infonnation contained herein. 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With respect to the publisher's copyright. material appearing in this book, prepared by individuals as part of their official duties as government employees. is only covered by this copyright to the extent permitted by the appropriate national regulations. CONTENTS Part I. Advances in Bone Marrow Transplant: Stem Cells and T-Cell Depletion 1. T-Cells, Graft-versus-Host Disease, and Graft-versus-Leukemia: New Approaches for Blood and Marrow Transplantation .................. . Richard Champlin, Sergio Giralt, and James Gajewski 2. Combined Use of Growth Factors to Stimulate the Proliferation of Hematopoietic Progenitor Cells after Autologous Bone Marrow Transplantation (ABMT) for Lymphoma Patients . . . . . . . . . . . . . . . . . . . .. II Roberto M. Lemoli, Alessandra Fortuna, Miriam Fogli, Gianantonio Rosti, Filippo Gherlinzoni, Giuseppe Visani, Lucia Catani, Alessandro Gozzetti, and Sante Tura 3. Long-Term Multilineage Development from Human Umbilical Cord Blood Stem Cells in a Novel SCID-hu Graft .............................. 21 Christopher C. Fraser, Hideto Kaneshima, Gun Hansteen, Madison Kilpatrick, Ronald Hoffman, and Benjamin P. Chen 4. Peripheral Blood Stem Cell Mobilization with G-CSF (Filgrastim) Alone for Autologous Transplant in Myeloid and Lymphoid Malignancies ......... 31 E. Archimbaud, M. Michallet, I. Philip, C. Sebban, P. Tremisi, G. Clapisson, A. Belhabri, and D. Fiere 5. Density Separation and Cryopreservation of Umbilical Cord Blood Cells: Evaluation of Recovery by Means of Short-and Long-Term Culture 37 Camillo Almici, Carmelo Carlo-Stella, John E. Wagner, and Vittorio Rizzoli 6. Economic Implications of High Dose Chemotherapy Programs with Autologous Stem Cell Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 45 Charles L. Bennett, Michael R. Bishop, and Subhash C. Gulati ix x Contents 7. CFU-GM Growth from Peripheral Blood Stem Cells (PBSC) before and after Cryopreservation: Comparison with Bone Marrow Cells ............... 53 M. Bonfichi, C. Brera, A. Balduini, E. P. Alessandrino, P. Bernasconi, D. Troletti, M. Boni, C. Castagnola, E. Brusamolino, G. Pagnucco, C. Perotti, L. Salvaneschi, and C. Bernasconi 8. Is There an Embryological Basis for the Association of Mediastinal Germ Cell Tumors and Hematologic Cancers? A Review . . . . . . . . . . . . . . . . . . . . . . .. 59 William J. Larsen 9. Autologous BMT for Treatment of Experimental Autoimmune Diseases ....... 69 D. W. van Bekkum and M. van Gelder 10. Peripheral Blood Precursor Cell Transplants across a Major Histocompatibility Barrier in Rabbits: Positive Effect of a Higher Number of Precursor Cells? 77 A. Gratwohl, H. Baldomero, L. John, A. Tichelli, A. Filipowicz, C. Nissen, and B. Speck II. Reticulocyte Parameters as Early Indicators of Hematopoietic Recovery after Bone Marrow Transplantation .................................... 83 M. Tommasi, G. d'Onofrio, G. Zini, P. Salutari, S. Sica, and G. Leone 12. Primordial Germ Cell-Derived Hemopoiesis: A New Concept for the Initiation of Hemopoiesis ................................................ 93 Ivan N. Rich and Frank Zimmermann 13. Monitoring of Serum HLA Class I Antigen Levels in Allogeneic Bone Marrow Transplantation ................................................ 101 Francesco Puppo, Sabrina Brenci, Massimo Ghio, Donatella Bignardi, Paola Contini, Andrea Bacigalupo, Maria T. Van Lint, Gilberto Filaci, Marco Scudeletti, Soldano Ferrone, and Francesco Indiveri 14. Correlation of ELISA-Measured Anti-HLA Class I IgG and IgG I Antibodies and First-Year Rejection Episodes ................................. 107 Jeffrey Regan, Francisco Monteiro, Daniel Speiser, Jorge Kalil, Ronald Kerman, Philippe Pouletty, and Roland Buelow 15. Inactivation or Down-Regulation of the Overstimulated, HLA-DR-(CD2R-, CD26-, CD38- and/or CD69-) Positive T Cell Subset Enables the Immunocompetent CeIls to Restore the Pre-Disease State: A Novel Technique ("Microimmunosurgery"), Based on a GvHD-Free GvLlGvT Effect, AIlows a Complete (100%) Eradication of Solid Tumors by an Indirect Attack on the Tumor-Protecting CD8+ HLA-DR+ Cells .......... lIS P. Leskovar and I. Vodenitcharov 16. European Cup Trial: A Randomized Trial Comparing the Efficacy of Chemotherapy with Purged or Unpurged Autologous Transplantation in Adults with Poor Risk Relapsed Follicular NHL: An EBMT Working Party Trial .................................................... 123 A. PorceIlini, H. Schouten, B. Stade, and R. KoIl Contents xi Part II. Clinical Update on Malignant Lymphoma and Myeloma: Mechanism/Therapy 17. Mechanisms of Chromosomal Translocations in Malignant Lymphomas ....... 127 Michael J. Uppenkamp, Heinz-Gert HOffkes, Peter Meusers, and Gunter Brittinger 18. Molecular Findings and Classification of Malignant Lymphomas ............. 135 Stefano A. Pileri, Claudio Ceccarelli, Elena Sabattini, Donatella Santini, Omella Leone, Stefania Damiani, Lorenzo Leoncini, and Brunangelo Falini 19. Mantle Cell Lymphoma: Genetic Lesions and Their Role in Classification and Progression ................................................... 145 G. Ott, M. M. Ott, J. Kalla, A. Helbing, B. Schryen, T. Katzenberger, J. Bartek, A. Durr, J. G. Muller, H. Kreipe, and H. K. Muller-Hermelink 20. Lymphoblastic Lymphoma in Adults .................................... 151 John Sweetenham 21. A New Non-Radioactive Method for Detection of Monoclonal Cell Populations in Patients with Burkitt's Lymphoma ............................... 159 Udo zur Stadt, Alfred Reiter, Jorg Tomeczkowski, and Karl-Walter Sykora 22. Oncogenes in the Pathogenesis of Multiple Myeloma ...................... 169 Paolo Corradini, Monica Astolfi, Marco Ladetto, Silvia Campana, Mario Boccadoro, and Alessandro Pileri 23. Expression and Regulation of c-kit Receptor and Proliferative Response to Stem Cell Factor in Childhood Lymphoma and Leukemia Cells ......... 173 J. Tomeczkowski, D. Frick, B. Schwinzer, A. Reiter, K. Welte, and K. W. Sykora 24. Growth Inhibition in IL-7 Receptor Positive Childhood Burkitt's Lymphoma Cells Is Not Due to Induction of Apoptosis .......................... 191 Karl W. Sykora, Jorg Tomeczkowski, Konstanze Kirchhoff, ElifYakisan, Alfred Reiter, and Karl Welte Part III. Update on Advancement in Leukemia 25. Expression of the Multidrug-Resistance Gene Product, P-Glycoprotein, in Adult Acute Myeloid Leukemia: Association with Stem Cell Antigen CD34 and Specific Cytogenetic Abnormalities ....................... 201 Elisabeth Paietta, Janet Andersen, Jorge Yunis, Jacob M. Rowe, Peter A. Cassileth, and Peter H. Wiernik, for the Eastern Cooperative Oncology Group 26. Characterization ofN-RAS Promoter Mutations in Leukemia ................ 207 Harry Hand, Jacqui Thorn, and Peter Molloy xii Contents 27. The Role of Anthracyclines in the Management of Adult Acute Lymphoblastic Leukaemia .................................................... 215 R. Bassan, T. Lerede, A. Rambaldi, E. Di Bona, G. Rossi, E. Pogliani, G. Lambertenghi-Deliliers, A. Porcellini, P. Coser, and T. Barbui 28. Collection ofbcr-abl Negative Peripheral Blood Progenitor Cells in Newly Diagnosed Patients with Chronic Myeloid Leukaemia ................. 221 N. Storey, A. L. Lennard, A. M. Dickinson, J. A. Irving, D. Rowe, D. Levett, J. Dunn, A. R. Cattan, and S. J. Proctor 29. CD34 Quantitative Flow Cytometry Study of the Blastic Population in Acute Leukemias .................................................... 227 Gian Matte<;l Rigolin, Francesco Lanza, and Gianluigi Castoldi 30. Cytokine Gene Expression in a Case ofB-Cell Chronic Lymphocytic Leukemia (B-CLL) with an Unusual Expansion ofT Cells at Presentation .......... 237 Athanasia Mouzaki, Vincent Kindler, Nicolette Bowers, Arlette Doucet, Maria Melachrinou, Maria-Christina Kyrtsonis, and Alice Kallinikou-Maniatis 31. Exploitation of Frequent p 16 Deletion in the Treatment of T Cell Acute Lymphoblastic Leukemia ........................................ 247 A. L. Yu, J. Chen, M. B. Diccianni, A. Batova, and J. Yu 32. Detection ofbcr-abl m-RNA in Single Progenitor Colonies by PCR: Comparison with Cytogenetics and PCR from Uncultured Cells ......... 257 Elisabeth Schulze, Rainer Krahl, Karin Thalmeier, and Werner Helbig 33. Quantitative RT-PCR ofPML-RARa Transcripts in Acute Promyelocytic Leukemia ..................................................... 269 Harry Hand, Francisca Springall, Tao Zeng, and Katrina Bradfield Part IV. Update on Role of HIV and Viruses in Hematopoiesis 34. AIDS-Related Non-Hodgkin Lymphomas: Molecular Genetics, Viral Infection, and Cytokine Deregulation ....................................... 277 Gianluca Gaidano, Cristina Pastore, Annunziata Gloghini, Daniela Capello, Gisella Volpe, Paolo Ghia, Giuseppe Saglio, and Antonino Carbone 35. Anti-HIV Viral Interference Induced by Retroviral Vectors Expressing a Non-Producer HIV-I Variant ...................................... 285 M. Federico, R. Bona, P. D'Aloja, M. Baiocchi, K. Pugliese, F. Nappi, C. Chelucci, F. Mavilio, and P. Verani 36. Suppression of Hematopoietic Support Function Is Associated with Over-Expression ofIL-4 and TGF~I in LP-BM5 MuLV Infected Stromal Cell Lines ..................................................... 293 Vincent S. Gallicchio, Kam-Fai Tse, Jennifer Morrow, and Nedda K. Hughes