Assessment of ASC specks as a putative biomarker of pyroptosis in myelodysplastic syndromes: an observational cohort study

Publication date: Available online 30 July 2018Source: The Lancet HaematologyAuthor(s): Ashley A Basiorka, Kathy L McGraw, Farnoosh Abbas-Aghababazadeh, Amy F McLemore, Nicole D Vincelette, Grace A Ward, Erika A Eksioglu, David A Sallman, Najla Al Ali, Eric Padron, Javier Pinilla-Ibarz, Rami Komrokji, Erico Masala, Valeria Santini, Olivier Kosmider, Michaela Fontenay, Pierre Fenaux, Lubomir Sokol, Sheng Wei, Brooke FridleySummaryBackgroundNLRP3 inflammasome-directed pyroptotic cell death drives ineffective haemopoiesis in myelodysplastic syndromes. During inflammasome assembly, the apoptosis-associated speck-like protein containing a CARD (PYCARD, commonly known as ASC) adaptor protein polymerises into large, filamentous clusters termed ASC specks that are released upon cytolysis. Specks are resistant to proteolytic degradation because of their prion-like structure, and therefore might serve as a biomarker for pyroptotic cell death in myelodysplastic syndromes.MethodsThis observational cohort study was done at the H Lee Moffitt Cancer Center (Tampa, FL, USA). Patients with myelodysplastic syndromes, healthy controls, and patients with non-myelodysplastic syndrome haematological cancers or type 2 diabetes were recruited. We used confocal and electron microscopy to visualise, and flow cytometry to quantify, ASC specks in peripheral blood and bone marrow plasma samples. Speck percentages were compared by t test or ANOVA, correlations were assessed by Spearman's rank correlation ...
Source: The Lancet Haematology - Category: Hematology Source Type: research