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Myelodysplastic syndromes: pathogenesis, functional abnormalities, and clinical implications Jacobs AJ Clin Pathol 1985[Nov]; 38 (11): 1201-17The myelodysplastic syndromes represent a preleukaemic state in which a clonal abnormality of haemopoietic stem cell is characterised by a variety of phenotypic manifestations with varying degrees of ineffective haemopoiesis. This state probably develops as a sequence of events in which the earliest stages may be difficult to detect by conventional pathological techniques. The process is characterised by genetic changes leading to abnormal control of cell proliferation and differentiation. Expansion of an abnormal clone may be related to independence from normal growth factors, insensitivity to normal inhibitory factors, suppression of normal clonal growth, or changes in the immunological or nutritional condition of the host. The haematological picture is of peripheral blood cytopenias: a cellular bone marrow, and functional abnormalities of erythroid, myeloid, and megakaryocytic cells. In most cases marrow cells have an abnormal DNA content, often with disturbances of the cell cycle: an abnormal karyotype is common in premalignant clones. Growth abnormalities of erythroid or granulocyte-macrophage progenitors are common in marrow cultures, and lineage specific surface membrane markers indicate aberrations of differentiation. Progression of the disorder may occur through clonal expansion or through clonal evolution with a greater degree of malignancy. Current attempts to influence abnormal growth and differentiation have had only limited success. Clinical recognition of the syndrome depends on an acute awareness of the signs combined with the identification of clonal and functional abnormalities.|Anemia, Refractory, with Excess of Blasts/etiology[MESH]|Animals[MESH]|Antineoplastic Agents/adverse effects[MESH]|Blood Cell Count[MESH]|Bone Marrow/pathology[MESH]|Cell Transformation, Neoplastic[MESH]|Cholecalciferol/therapeutic use[MESH]|Chromosome Aberrations[MESH]|Chromosome Disorders[MESH]|Colony-Forming Units Assay[MESH]|Colony-Stimulating Factors/therapeutic use[MESH]|DNA/biosynthesis[MESH]|Hematopoietic Stem Cells/drug effects[MESH]|Humans[MESH]|Leukemia, Radiation-Induced/pathology[MESH]|Leukemia/chemically induced[MESH]|Mice[MESH]|Myelodysplastic Syndromes/diagnosis/drug therapy/*etiology[MESH]|Oncogenes[MESH]|Preleukemia/etiology[MESH]|Rats[MESH]|Tretinoin/therapeutic use[MESH] |
