BONE MARROW MONOCYTES AND DERIVED DENDRITIC CELLS FROM MYELODYSPLASTIC PATIENTS HAVE FUNCTIONAL ABNORMALITIES ASSOCIATED WITH DEFECTIVE RESPONSE TO BACTERIAL INFECTION

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell diseases characterized by dysplasia of one or more hematologic lineages and a high-risk of developing acute myeloid leukemia (AML). MDS patients have recurrent bacterial infections and abnormal expression of CD56 by monocytes. We investigated MDS patients’ bone marrow CD56+/CD56- monocytes and their in vitro derived dendritic cell (DCs) populations in comparison to cells obtained from disease-free subjects. We found that monocytes from MDS patients, irrespective of CD56 expression, have reduced phagocytosis activity and low expression of genes involved in triggering immune responses, regulation of immune and inflammatory response signaling pathways, and in the response to lipopolysaccharide. Dendritic cells (DCs) derived in vitro from MDS monocytes failed to develop dendritic projections and had reduced expression of HLA-DR and CD86 suggesting that antigen processing and T cell activation capabilities are impaired. In conclusion, we identified in both CD56+ and CD56- monocytes from MDS-patients several abnormalities that may be related to the increased susceptibility to infections observed in these patients. The aim of the present study was to study CD56+ and CD56- bone marrow monocytes and derived DCs obtained from MDS patients and free-disease individuals. We analyzed the monocyte populations by flow cytometry, their morphological aspects and phagocytic activity, as well as gene expression patterns and cell surface markers. Taken together, alterations in the expression of MHC-class II and co-stimulatory molecules, toll-like receptors and cytokine gene expression, suggest functional abnormalities within the monocyte population that may contribute to deficient response to bacterial infection, a common feature in MDS patients.