LAUSR

Myelodysplastic syndrome (MDS) is characterized by persistent cytopenias and evidence of morphologic dysplasia in the bone marrow (BM). Excessive hematopoietic programmed cell death (PCD) and inflammation have been demonstrated in MDS patients' bone marrow and are thought to play an important role in the pathogenesis of the disease. Necroptosis is a major pathway of PCD that incites inflammation; however, the role of necroptosis in human MDS has not been extensively investigated. To assess PCD status in newly diagnosed MDS, we performed immunofluorescent staining with computational image analysis of formalin fixed paraffin embedded BM core biopsies using cleaved CASPASE 3 (apoptosis marker) and necroptosis markers (RIPK1, pMLKL). MDS but not normal controls or de novo AML demonstrated significantly increased expression of RIPK1 and pMLKL but not cleaved CASPASE 3, which was most evident in morphologically low-grade MDS (<5% BM blasts) and in MDS with low IPSS-Risk score. RIPK1 expression highly correlated with the distribution of CD71+ erythroid precursors but not with CD34+ blast cells. We found that necroptosis is upregulated in early/low-grade MDS relative to normal controls, warranting further study to define the role of necroptosis in the pathogenesis of MDS and as a potential biomarker for the diagnosis of low-grade MDS.