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

Cancer Cell. 2008 Oct 7;14(4):335-43. doi: 10.1016/j.ccr.2008.08.014.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Biomarkers, Tumor
  • STAT5 Transcription Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • JAK2 protein, human
  • Janus Kinase 2