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Michael R. Loken and Denise A. Wells

Flow cytometry quantifies the gene product expression on hematopoietic cells, permitting the identification of all cells within a bone marrow aspirate and classifying them according to lineage and maturational stage. The relationships in the expression of multiple markers on myeloblasts, maturing monocytes, and myeloid cells suggests that development of these cells is a stepwise process in which genes are not only turned on or off, but are up- and down-regulated at the junctions between stages. In neoplastic processes, a loss of coordination of these steps is seen, resulting in the abnormal relationships identified by flow cytometry. In myelodysplastic syndromes, the abnormal patterns can be identified on both the immature myeloblasts and maturing myeloid cells and monocytes. The detection of these abnormalities is useful in diagnosing myelodysplasia but requires a detailed understanding of the expression of these gene products to discriminate neoplastic transformation from a stressed marrow. Although the patterns of antigen expression for normal hematopoiesis are precisely defined, each patient with a neoplastic transformation has a unique repertoire of abnormalities that may evolve as the disease progresses. Therefore, scoring systems, in which the abnormalities are counted, provide a means for determining the extent of dysregulation at all the maturational steps, thereby determining a “distance from normal” for a patient at a specific time in the disease course. This is useful, not only to facilitate diagnosis, but to provide prognostic information that may be complementary to the conventional classification schemes and scoring systems.