Surface marker abnormalities in myelodysplastic syndromes

Abstract

BACKGROUND AND OBJECTIVE: The myelodysplastic syndromes (MDS) are clonal stem cell disorders associated with a variety of abnormalities of mature and maturing cells, including surface antigen abnormalities. Granulocytes and monocytes function as members of the immune system. Surface antigens serve as biological sensors allowing various cells to interact with different stimuli. Abnormalities of surface antigens may be associated with defective cell function and may indicate a more severe or more advanced stage of the disease. INFORMATION SOURCES: The author has a great interest in bone marrow changes in MDS and has several previous publications in this field. In addition, relevant articles published since 1966 were retrieved using Medline of English literature and were included. STATE OF THE ART AND PERSPECTIVES: Several surface antigens in MDS have shown abnormal expression either in the intensity of fluorescence or the percentage of positive cells. These abnormalities include increased, decreased or lineage-aberrant expression. Abnormalities of several surface markers have prognostic significance. MDS patients with a low percentage of bone marrow cells expressing CD11b had a higher risk of evolution to acute myeloid leukemia and shorter survival compared to patients with more than 53% of marrow cells expressing CD11b (29 weeks versus 160 weeks). On the other hand, an increased percentage of bone marrow cells expressing early or immature markers, such as CD 13, CD33, CD34 and HLA-DR, has been associated with a worse outcome and with progression to a higher risk MDS or to acute myeloid leukemia. However, there are numerous discrepancies and inconsistencies in the literature when reviewing surface marker changes in MDS. These discrepancies may be related, at least in part, to the presence of an intracellular storage compartment of numerous surface antigens in the granulocytes and monocytes. Because of these storage pools, the techniques of preparing more mature granulocytes and monocytes, such as density gradient separation, and the interpretation of results must be carefully evaluated. Furthermore, various methods have been used to express abnormal results including percentage of positive or negative cells, fluorescent intensity (FI) of individual patients or a group of patients using a mean fluorescent channel (256 or 1024 channel mode), and finally the expression of FI as molecules of equivalent soluble fluorochromes or antibody binding capacities. Several mechanisms may be involved in the abnormal expression of surface antigens in MDS including defective granulopoiesis, defective intracellular storage pool, abnormal membrane of cytoplasmic granules, and the effect of high levels of marrow cytokines such as tumor necrosis factor alpha and transforming growth factor-beta. Standardization of the methods of preparing and studying mature and maturing granulocytes and monocytes in MDS has to be achieved in order to produce comparable results, thus allowing surface marker studies to be utilized as diagnostic and prognostic tools in MDS.