Recent Advances in Cell Biology of Acute Leukemia : Impact on Clinical Diagnosis and Therapy

The development of new techniques such as immuno­ phenotyping, cytogenetic investigations and, more recently, molecular studies has considerably increased our diagnostic repertoire and broadened our ideas about the biology of acute leukemias. While immunophenotyping with mono­ clonal antibodies has yielded increased diagnostic precision and made it possible to develop a highly reproducible classification of acute leukemias based on cell-biological features, further insights have been gained into the patho­ genetic mechanisms involved in leukemogenesis by means of cytogenetic detection of acquired structural chromosomal abnormalities. Analysis of the leukemia-associated chromo­ somal breakpoints using molecular techniques can now pinpoint many genomic sites essential for normal develop­ ment and maturation of hematopoietic cells but functionally disrupted in leukemic cells. The main goal of the international workshop that we held in Berlin with a select group of scientists and clinicians involved in leukemia research was to describe the state of the art and new developments in the immunologic, cytogenetic, and molecular characterization of acute leukemias and to discuss the clinical importance of cell­ biological features. After introductory survey lectures dealing with the immunological and molecular-biological characteristics of normal vs. malignant lymphatic and myeloid progenitor cells, the workshop centered on con­ tributions characterizing the immunophenotype and both numerical and structural chromosomal abnormalities in acute leukemias.

I. Hematopoietic Differentiation.- Differentiation of Physiological and Malignant Cells of the B-Cell System.- Expression of B-Cell-Associated Antigens During B-Cell Ontogeny.- Normal and Aberrant T-Cell Receptor Protein Expression in T-Cell Acute Lymphoblastic Leukemia.- Flow Cytometric Analysis of Intracellular Myeloperoxidase and Lactoferrin in Leukemia Diagnosis.- II. Phenotypic Heterogeneity in Acute Leukemias: Immunological Characterization and Clinical Relevance.- Immunological, Ultrastructural and Molecular Features of Unclassifiable Acute Leukaemia.- Incidence and Clinical Relevance of Myeloid Antigen-Positive Acute Lymphoblastic Leukemia.- Myeloid-Associated Antigen Expression in Childhood Acute Lymphoblastic Leukemia.- Contribution of Electron Microscopy to the Classification of Minimally Differentiated Acute Leukemias in Children.- III. Biological and Clinical Significance of Cytogenetic Abnormalities in Acute Leukemias.- Molecular Cytogenetic Applications in Leukemias.- Cytogenetic Abnormalities Associated with Childhood Acute Myeloblastic Leukemia.- DNA Aneuploidy in Childhood Acute Lymphoblastic Leukemia: Relation to Clinical Determinants and Prognosis within Four Consecutive BFM Trials.- Clinical Significance of Cytogenetic Studies in Childhood Acute Lymphoblastic Leukemia: Experience of the BFM Trials.- Chromosomal Abnormalities in Adult Acute Lymphoblastic Leukemia: Results of the German ALL/AUL Study Group.- IV. Minimal Residual Disease in Acute Leukemias: Detection and Immunotherapeutic Strategies.- Molecular Genetic Techniques for Detection of Minimal Residual Disease in Acute Lymphoblastic Leukemia: Possibilities and Limitations.- Immunophenotypic and Immunogenotypic Detection of Minimal Residual Disease in Acute Lymphoblastic Leukemia.- Detection of Aberrant Antigen Expression in Acute Myeloid Leukemia by Multiparameter Flow Cytometry.- Detection of Residual Leukemic Cells in Adult Acute Lymphoblastic Leukemia by Analysis of Gene Rearrangements and Correlation with Early Relapses.- Interleukin-2-Based Immunotherapy in the Management of Minimal Residual Disease in Acute Leukemia Patients.- Preclinical Studies of T-Cell-Mediated Immune Responses Against Autologous Tumor Cells in Patients with Acute Leukemia.- Susceptibility of Human Leukemia Cells to Allogeneic and Autologous Lymphokine-Activated Killer Cells and Its Augmentation by Exposure of Leukemia Target Cells to Cytotoxic Drugs In Vitro and In Vivo.- V. Immunophenotypic and Molecular Genetic Characterization of Acute Lymphoblastic Leukemia: Biological and Clinical Implications.- Regulation of Protooncogenes and Cytokine Genes in Acute Lymphoblastic Leukemia.- Cellular Drug Sensitivity of Immunophenotypic Subgroups of Childhood Acute Lymphoblastic Leukemia.- Use of Clinical and Laboratory Features to Define Prognostic Subgroups in B-Precursor Acute Lymphoblastic Leukemia: Experience of the Pediatric Oncology Group.- Incidence and Prognostic Significance of Immunophenotypic Subgroups in Childhood Acute Lymphoblastic Leukemia: Experience of the BFM Study 86.- Incidence, Clinical and Laboratory Features, and Prognostic Significance of Immunophenotypic Subgroups in Acute Lymphoblastic Leukemia: The GEIL Experience.- Incidence and Prognostic Significance of Immunophenotypic Subgroups in Childhood Acute Lymphoblastic Leukemia: The Experience of the AIEOP Cooperative Study.- Mutations in the Regulatory Domains of bcr/abl-Positive Leukemias Detected by Solid-Phase Automated DNA Sequencing.- VI. Leukemic Cell Characterization in Acute Myeloid Leukemia: Biological and Clinical Implications.- Clonal Analysis of n-ras Gene Activation in Acute Myeloid Leukemia.- Human Stem Cell Factor is a Growth Factor for Myeloid Leukemia Cells.- Morphologic Basis for the MIC Classification in Acute Myeloid Leukemia.- Molecular Genetics of the t(15;17) Translocation in Acute Promyelocytic Leukemia.- Immunophenotype of Hematologic Neoplasms with a Translocation t(8;21).- Diagnostic and Prognostic Importance of Immunophenotyping in Adults with Acute Myeloid Leukemia.- Immunophenotype of Acute Myeloid Leukemia: Correlation with Morphological Characteristics and Therapy Response.- Multiparameter Analysis of Blast Cells in Patients with Acute Leukemia Following a Primary Myelodysplastic Syndrome.