A workshop on "MOLECULAR ASPECTS OF MYELOID STEM CELL DEVELOPMENT" was held at the Historic Inns in Annapolis, MD during April 30-May 3, with approximately 70 persons attend ing. The enormous success of this meeting was attributable to the recent outburst of information generated from two areas of study: transcriptional regulation of developmentally important myeloid genes and molecular dissection of chromosomal abnormalities in human myeloid leukemias. It was reassuring that studies of normal myelopoiesis and abnormal myelopoiesis, as observed in dys plasias and neoplasia, are revealing several interrelated mechan isms of gene regulation. However, great challenges await us as we try to determine how these and other mechanisms in this intricate system orchestrate the ultimate fate of cells e. g. proliferation, differentiation or apoptosis. This volume of Current Topics in Micro biology encapsulates many of the key aspects of the workshop summarizing research over the past few years on the ontogeny and pathology of myeloid cells. Investigations into the complex process of normal myeloid cell . maturation were first made possible through development of in vitro clonigenic assays. These established the relationships of colony stimulating factors, interleukins and their combinations to the specific fates of myeloid progenitors derived from the bone , marrow and spleen. Molecular studies became feasible, however, through the later establishment of several cell culture systems in volving immortalized cells which, under the proper induction, could fairly accurately recapitulate the myelopoietic process.
Regulation of Myeloid Differentiation, Growth Arrest and Apoptosis.- Molecular Control of Development in Normal and Leukemic Myeloid Cells by Cytokines, Tumor Suppressor and Oncogenes.- Retinoic Acid Receptors in Hematopoiesis.- Role of c-myc in Myeloid Differentiation, Growth Arrest and Apoptosis.- Self Renewal and Differentiation in Primary Avian Hematopoietic Cells: An Alternative to Mammalian in Vitro Models?.- Receptors and Signal Transduction.- The Effect of C-raf Antisense Oligonucleotides on Growth Factor-Induced Proliferation of Hematopoietic Cells.- Protein Kinase C-?, an Important Signaling Molecule in the Platelet-Derived Growth Factor ? Receptor Pathway.- Novel Adapter Proteins that Link the Human GM-CSF Receptor to the Phosphatidylinositol 3-Kinase and Shc/Grb2/ras Signaling Pathways.- Myb: Proliferation and Maintenance of Stage Specific Genes.- Functional Analysis of the c-myb Proto-Oncogene.- Structure and Function of the Proteins Encoded by the myb Gene Family.- The c-Myb Negative Regulatory Domain.- Myeloid-Specific Transcription.- Terminal Myeloid Gene Expression and Differentiation Requires the Transcription Factor PU.1.- A Role for STAT Family Transcription Factors in Myeloid Differentiation.- Regulation of C/EBP?/NF-M Activity by Kinase Oncogenes.- Function of PU.1 (Spi-1), C/EBP, and AML1 in Early Myelopoiesis: Regulation of Multiple Myeloid CFS Receptor Promoters.- Regulation of Immature Myeloid Cell Differentiation by PEBP2/CBF, MYB, C/EBP and ETS Family Members.- Hematopoietic Transcriptional Regulation by the Myeloid Zinc Finger Gene, MZF-1.- Coordinate Regulation of Neutrophil Secondary Granule Protein Gene Expression.- lnterleukin-5 Receptor ? Subunit Gene Regulation in Human Eosinophil Development: Identification of a Unique Cis-Element that acts lie an Enhacer in Regulating Activity of the IL-5R? Promoter.- Molecular Aspects of Myeloid Leukemia. I. Murine Studies.- Retroviral Insertional Mutagenesis in Murine Promonocytic Leukemias:c-myband Mm/1..- Molecular Analysis and Characterization of Two Myeloid Leukemia Inducing Murine Retroviruses.- Molecular Analysis of Evil, a Zinc Finger Oncogene Involved in Myeloid Leukemia.- Activation of Stat-related DNA-binding Factors by Erythropoietin and the Spleen Focus-Forming Virus.- The Neurofibromatosis Type 1 (NF1) Tumor Suppressor Gene and Myeloid Leukemia.- Molecular Aspects of Myeloid Leukemia. II. Human Studies.- Rearrangement of the AML1/CBFA2 Gene in Myeloid Leukemia with the 3;21 Translocation:Expression of Co-Existing Multiple Chimeric Genes with Similar Functions as Transcriptional Repressors, but with Opposite Tumorigenic Properties.- Transcriptional Regulation by the t(8;21 )Fusion Protein, AML-1/ETO.- The Mixed Lineage Leukemia (MLL) Protein Involved in 11 q23 Translocations Contains a Domain that Binds Cruciform DNA and Scaffold Attachment Region (SAR) DNA.- Pathogenetic Role of the PML/RAR? Fusion Protein in Acute Promyelocytic Leukemia.- Involvement of the TEL Gene in Hematologic Malignancy by Diverse Molecular Genetic Mechanisms.- Transforming Properties of the Leukemic Inv(16) Fusion Gene CBFB-MYH11..