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Chapter 1
Molecular basis of hematology
Basic concepts
Advances in recombinant DNA technology over the past 25 years have substantially altered our view of biologic processes and have immediate relevance to our understanding of both normal hematopoietic cell function and hematologic pathology. A complete review of molecular genetics is beyond the scope of this text, but the following is intended as a brief review of the concepts of the molecular biology of the gene and an explanation of the terminology necessary for understanding the role of molecular biology in breakthrough discoveries, as well as emerging diagnostic and therapeutic approaches in hematology. The concepts outlined in the following are Anatomy of the gene Structure of DNA Structure of the gene Flow of genetic information Transcription Translation Control of gene expression The Human Genome Project and HapMap
Analytic techniques
Digestion and separation of nucleic acids Hybridization techniques Cytogenetic techniques Conventional cytogenetics Fluorescence in situ hybridization Comparative genomic hybridization Polymerase chain reaction DNA microarray technology Proteomics Transgenic and knockout mice
Clinical applications of DNA technology in hematology
Applications to prenatal diagnosis of hemoglobinopathies Screening with oligonucleotides and PCR Applications to the diagnosis and treatment of hematologic malignancies Gene rearrangement studies in lymphoproliferative disease Identification of cryptic translocation in pediatric acute lymphoblastic leukemia: prognostic significance Nucleophosmin mutations in acute myeloid leukemia Bcr-abl: the CML versus ALL diagnostic dilemma Monitoring minimal residual disease in CML Minimal residual disease detection in lymphoma Expression profiling: applications to diagnosis and treatment Pharmacogenomics and treatment of acute lymphoblastic leukemia Applications to stem cell transplantation HLA typing for stem cell transplantation Analysis of bone marrow engraftment Applications to novel therapies Antisense and RNA interference therapy Gene therapy
Glossary
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