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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, an introduction to epigenetics and genomics, an outline of noncoding RNAs, and an explanation of the terminology necessary for understanding the role of molecular biology in breakthrough discoveries. Emerging diagnostic and therapeutic approaches in Anatomy of the gene Structure of DNA Structure of the gene Epigenetics DNA methylation Flow of genetic information Transcription Translation Control of gene expression Genomics
Analytic techniques
Digestion and separation of nucleic acids Hybridization techniques Cytogenetic techniques Conventional cytogenetics Fluorescence in situ hybridization Comparative genomic hybridization SNP chips Sequence-based studies Polymerase chain reaction DNA microarray technology: expression arrays Proteomics Transgenic and knockout mice
Clinical applications of DNA technology in hematology
Applications to germline (inherited) mutations Screening with oligonucleotides and PCR Applications to somatic (acquired) mutation Gene rearrangement studies in lymphoproliferative disease: T-cell and B-cell mutations Identification of cryptic translocation in pediatric acute lymphoblastic leukemia: prognostic significance Nucleophosmin mutations in acute myeloid leukemia Monitoring minimal residual disease in CML Minimal residual disease detection in lymphoma Expression profiling: applications to diagnosis and treatment Pharmacogenomics and treatment of ALL 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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