Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates.
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.
Kotecha
Nikesh
N
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Flores
Nikki J
NJ
Irish
Jonathan M
JM
Simonds
Erin F
EF
Sakai
Debbie S
DS
Archambeault
Sophie
S
Diaz-Flores
Ernesto
E
Coram
Marc
M
Shannon
Kevin M
KM
Nolan
Garry P
GP
Loh
Mignon L
ML
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D018450:Disease Progression; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D010766:Phosphorylation; D012008:Recurrence; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D050799:STAT5 Transcription Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2