Immunohistochemical Analysis of Inflammasome Signaling Component Expression Among Patients with Low Risk and High Risk Myelodysplastic Syndrome Using Tissue Microarray

Background: Myelodysplastic syndromes (MDS) are characterized by aberrant maturation, ineffective hematopoiesis, cytopenias, and progression to acute myeloid leukemia. MDS pathogenesis is multifactorial and potentially linked to constitutive innate immune stimulation converging upon the NLRP3 inflammasome to induce pyroptosis, a caspase-1 dependent cell death. Inflammasome assembly is initiated by both cell-extrinsic stimuli including S100A9, the TLR4 and CD33 ligand, and cell-intrinsic danger signals licensing caspase-1 which activates IL1b and beta-catenin resulting in cell death and increased cellular proliferation leading to maturation and differentiation blocks. Further, EYA2 has been suggested to be an inflammasome activator, whereas PLA2 has been suggested to be an inhibitor. Recent work demonstrates immunohistochemistry (IHC) may be utilized to assess expression of inflammasome components. The purpose of the present study is to compare inflammasome component expression among patients with low and high risk MDS and correlate these findings with clinical outcome data.