Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates

单细胞分析可识别髓系恶性肿瘤中异常的 STAT5 激活,并具有特定的临床和生物学相关性

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作者:Nikesh Kotecha, Nikki J Flores, Jonathan M Irish, Erin F Simonds, Debbie S Sakai, Sophie Archambeault, Ernesto Diaz-Flores, Marc Coram, Kevin M Shannon, Garry P Nolan, Mignon L Loh

Abstract

Progress in understanding the molecular pathogenesis of human myeloproliferative disorders (MPDs) has led to guidelines incorporating genetic assays with histopathology during diagnosis. Advances in flow cytometry have made it possible to simultaneously measure cell type and signaling abnormalities arising as a consequence of genetic pathologies. Using flow cytometry, we observed a specific evoked STAT5 signaling signature in a subset of samples from patients suspected of having juvenile myelomonocytic leukemia (JMML), an aggressive MPD with a challenging clinical presentation during active disease. This signature was a specific feature involving JAK-STAT signaling, suggesting a critical role of this pathway in the biological mechanism of this disorder and indicating potential targets for future therapies.

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