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

Kotecha N, Flores NJ, Irish JM, Simonds EF, Sakai DS, Archambeault S, Diaz-Flores E, Coram M, Shannon KM, Nolan GP, Loh ML
Cancer Cell. 2008 14 (4): 335-43

PMID: 18835035 · PMCID: PMC2647559 · DOI:10.1016/j.ccr.2008.08.014

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.

MeSH Terms (19)

Adult Biomarkers, Tumor Cell Proliferation Cells, Cultured Child Disease Progression Flow Cytometry Gene Expression Regulation, Neoplastic Granulocyte-Macrophage Colony-Stimulating Factor Humans Janus Kinase 2 Leukemia, Myelomonocytic, Juvenile Myeloproliferative Disorders Neoplasm Staging Phosphorylation Recurrence Signal Transduction STAT5 Transcription Factor Treatment Outcome

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