Książki

This book has been written from two points of view: firstly, from the viewpoint of those who are involved in the diagnosis and treatment of lymphoid malignancies, who must meet the challenge of integrating the new biological insights into their knowledge of these diseases; and secondly, from the viewpoint of those who are involved in basic biological approaches to malignancy and immunology, who wish to know more about the function of the lymphoid tissues and their malignant diseases. Neoplasia of lymphocytes is a focus for considering many of the most important biological advances impinging on cancer in the past two or three decades, because malignant lymphoproliferative diseases offer unequalled opportunities for studying many aspects of cancer. We probably know more about lymphocytes than other normal cells because of the ease with which they can be obtained. For the same reason we probably know more about malignant lymphocytes. One or other aspect of most of the momentous advances in biology of the past two or three decades has implications for lymphoid malignancies: hybridoma technology and the use of monoclonal antibodies, gene technology, the understanding of oncogenes and growth factors in the control of growth and differentiation, insights into causation of cancer by potent tumour promoters such as the phorbol esters and by viruses, and knowledge of the control of growth function of lymphocytes themselves. Conversely, many of the advances in understanding lym phocytic leukaemias and lymphomas have implications for other cancers.

Essential Oncology of the Lymphocyte

1 Cancer Biology.- Development of Cancers from Single Cells.- Diversity of Tumour Cells.- Differentiation of Malignant Cells.- 2 Derangement of the Genome as a Cause of Cancer.- The Chromosomes.- Chromosomal Abnormalities in Cancer.- Susceptibility to Chromosome Damage and Cancer.- Constitutional Cytogenetic Abnormalities.- Fragile Sites.- 3 Derangements of the Mechanisms Controlling Growth.- Cell Cycle.- Signal Transduction.- Immortalisation and Transformation.- Mechanisms Leading to Autonomous Growth.- Differentiation Arrest.- 4 Multiple Steps in the Genesis of a Cancer.- Initiation.- Promotion.- Tumour-promoting Phorbol Esters.- Progression.- Conclusions.- 5 Multifactorial Aetiology of Cancers.- Population and Familial Factors.- Carcinogens.- Radiation.- Viruses.- Viruses in the Causation of Animal Cancers.- Viruses in the Causation of Human Cancers.- Immunodepression and Immunosuppression.- Prolonged Antigenic Stimulation.- 6 Oncogenes.- Translation Products of Oncogenes.- Oncogene Products with Protein Kinase Activity.- GTP-binding Oncogene Products.- Oncogenes Whose Products Bind to DNA.- Oncogene Product with Growth Factor Activity.- Oncogenes Encoding Receptors for Growth Factors.- Oncogenes Whose Products have Undefined Function.- Some Important Non-human Oncogenes.- Aberrations of Oncogenes in Cancer.- Proteins Homologous to Oncogene Products.- Transgenic Mice.- Oncogenes in Human Tumours.- Multiple Oncogene Expression.- Conclusions.- 7 Growth Factors.- Mechanisms of Action of Growth Factors.- Growth Factors in Malignant Transformation.- Growth Factors for Haematopoietic Cells.- Transforming Growth Factor ?.- Transforming Growth Factor ?.- Epidermal Growth Factor.- Platelet-derived Growth Factor.- Bombesin.- Insulin.- Insulin-like Growth Factor I.- Insulin-like Growth Factor II.- Nerve Growth Factor.- Chalones and Other Antiproliferative Factors.- Conclusions.- 8 The Lymphoid Tissues.- Origin of Lymphocytes.- T Lymphocytes.- B Lymphocytes.- NK, ADCC and Lymphokine-activated Killer Cells.- Accessory Cells.- Activation of Macrophages.- Lymphoid Organs and Immunological Function.- Lymphocyte Circulation.- Organisation of Immunological Function.- 9 The Major Histocompatibility Complex.- Tissue Distribution of MHC Products.- MHC Gene Products and Their Specificities.- Immunoregulatory Function of the MHC.- Mixed Lymphocyte Reaction.- Graft Versus Host Reaction.- Association of Diseases with MHC Phenotype.- Conclusions.- 10 T Cell Differentiation.- The Thymus.- T Lymphocytes in Bone Marrow.- T Cells in Lymph Nodes.- T Cell Subsets.- T Cell Subsets Defined by Monoclonal Antibodies.- T Cell Receptor.- Genetic Mechanisms in T Cell Differentiation.- T Cell Activation.- Signal Transduction in T Cell Activation.- 11 B Cell Differentiation.- Antigen-independent B Cell Differentiation.- B Lymphocyte Differentiation in Postnatal Life.- Antigen-dependent B Cell Differentiation.- B Cell Subsets.- Immunoglobulin.- Genetic Mechanisms in B Cell Differentiation.- Organisation of Immunoglobulin Genes.- Rearrangement of B Cell Genes During Ontogeny.- Human Heavy Chain Gene Organisation.- Light Chain Organisation.- Isotype Switch.- 12 B Cell Activation.- T Cells in B Cell Activation.- Accessory Cells in B Cell Activation.- B Cell Activation by Cross-linking Immunoglobulin.- Soluble Factors in B Cell Activation.- Type A Factors.- Type B Factors (BCGFs).- Type C Factors (BCDFs).- Transferrin.- Interferon.- Other Factors.- Cellular Events in B Lymphocyte Activation.- Conclusions.- 13 Immunoregulatory Mechanisms.- Systems Controlling Immunological Function.- Suppressor Mechanisms.- Idiotypes.- Idiotypes on T Cells.- Idiotypic Regulatory Network.- Immunological Tolerance.- Regulatory Mechanisms in B Cell Malignancies.- 14 Technology of Investigation and Diagnosis.- Hybridoma Technology and Monoclonal Antibodies.- Principles of Hybridoma Technology.- Gene Cloning.- Gene Probing.- Immunodiagnostic Methods.- Collection of Specimens.- Immunological Methods.- Rosette Formation.- Immunofluorescence on Cryostat Sections.- Immunohistochemical Methods.- Paraffin Sections.- Cryostat Sections.- Imprints and Cytocentrifuge Preparations.- Histochemical Stains.- Periodic-acid Schiff.- Non-specific Esterase.- Acid Phosphatase.- Tartrate-resistant Acid Phosphatase.- Alkaline Phosphatase.- Other Enzyme Reactions.- Flow Cytometry.- Ultrastructural Analysis.- Conclusions.- 15 B Cell Neoplasia.- Immunological Abnormalities in Lymphoid Malignancies.- Chromosomal Abnormalities in B Cell Malignancies.- Oncogene Activation in B Cell Neoplasia.- Immunoglobulin Gene Rearrangements.- 16 B Cell Leukaemias.- Acute Lymphoblastic Leukaemia.- Phenotype of ALL Cells.- Prognosis in ALL.- B-Chronic Lymphocytic Leukaemia.- Lymphocyte Kinetics.- Morphology.- Phenotype.- Cellular Abnormalities in CLL.- Malignant Stem Cell.- B Cell Prolymphocytic Leukaemia.- Morphology and Phenotype.- Hairy Cell Leukaemia.- Morphology and Phenotype.- Bone Marrow in HCL.- Spleen and Liver in HCL.- Chronic Cold Agglutinin Disease.- Lymphoplasmacytoid Lymphoma.- Plasma Cell Dyscrasias.- Multiple Myeloma.- Malignant Stem Cell.- Plasma Cell Leukaemia.- Localised Plasmacytoma.- Solitary Plasmacytoma of Bone.- Extramedullar Plasmacytoma.- Monoclonal Gammopathy of Undetermined Significance.- Heavy Chain Diseases.- Lymphosarcoma Cell Leukaemia.- 17 B Cell Lymphomas.- B Cell Lymphomas of the Deep Cortex.- Well-differentiated Lymphocytic Lymphoma.- Plasmacytoid Lymphocytic Lymphoma.- B Immunoblastic Sarcoma.- B Cell Lymphomas of the Superficial Cortex.- Follicular Centre Cell Lymphoma.- Small Follicular Centre Cell Proliferations.- Mixed Follicular Centre Cell Proliferations.- Large Follicular Centre Cell Proliferations.- Signet-ring Cell Lymphoma.- Phenotype of Follicular Centre Cell Lymphomas.- Intermediate and Mantle Zone Lymphomas.- B Cell Lymphomas of the Medulla: Plasmacytoma.- Undifferentiated B Cell Lymphomas.- Extranodal B Cell Lymphomas.- Hodgkin's Disease.- 18 T Cell Neoplasia.- Chromosomal Abnormalities in T Cell Malignancies.- Gene Rearrangements in T Cell Malignancies.- Immunoglobulin Genes in T Cell Malignancies.- 19 T Cell Leukaemias and Lymphomas.- T Cell Neoplasms of the Bone Marrow Compartment.- T Acute Lymphoblastic Leukaemia.- T Prolymphocytic Leukaemia.- T Hairy Cell Leukaemia.- T Cell Chronic Lymphocytic Leukaemia.- T? Lymphoproliferative Disease.- Adult T Cell Leukaemia/Lymphoma.- T Cell Neoplasms of the Thymic Compartment.- Lymphoblastic Lymphoma.- T Cell Neoplasms of the Peripheral Compartment.- Cutaneous T Cell Lymphomas.- Node-based T Cell Lymphoma.- Polymorphous Type.- Monomorphous Type.- Immunological Phenotypes.- Conclusions.- 20 Treatment, Treatment Failure and Future Possibilities.- Treatment Failure Exemplified by Lymphocytic Leukaemia.- Immunotherapy.- Monoclonal Antibodies.- Immunotoxins.- Antibodies Against Growth Factor Receptors.- Adoptive Immunity with Cytotoxic T Cells.- Activated Macrophages.- Cytokines and Other Biological Agents.- Interferon.- Tumour Necrosis Factor.- Thymic Cytokines.- New Drugs and Other Treatments.- Cyclosporin.- Purine and Pyrimidine Analogues.- Hyperthermia.- Vaccines Against HTLV.- Conclusions.