O-010 Prognostic factors of response to azacitidine (AZA) in low-risk MDS resistant to erythroid stimulating agents (ESA). The GFM Azaepo 08 study

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Conclusions: Our data demonstrate that HSCs are disease-initiating cells in MDS. While MDS HSCs exhibit relatively few functional differences from their normal counterparts, committed myeloid progenitors in low-risk MDS exhibit numerous alterations including loss of GMPs, upregulation of CRT, and increased phagocytosis by macrophages, with increased expression of CD47 and decreased phagocytosis associated with disease progression. These findings are consistent with a model in which committed progenitors in MDS undergo molecular alterations that promote programmed cell removal, thereby resulting in the cytopenias that characterize MDS, but this mechanism does not appear to be critical for disease maintenance by HSCs.