Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia

D. Hasegawa, C. Bugarin, M. Giordan, S. Bresolin, D. Longoni, C. Micalizzi, U. Ramenghi, A. Bertaina, G. Basso, F. Locatelli, A. Biondi, G. T. Kronnie, G. Gaipa

Research output: Contribution to journalArticle

Abstract

To diagnose juvenile myelomonocytic leukemia (JMML) is sometimes challenging, because around 10% of patients lack molecular abnormalities affecting Ras-MAPK (mitogen-activated protein kinase) pathway and other diseases such as cytomegalovirus infection can mimic clinical signs of JMML. In order to validate a phospho-specific flow cytometry assay assessing phospho-signal transducer and activator of transcription factor 5 (p-STAT5) as a new diagnostic tool for JMML, we examined 22 samples from children with JMML and 47 controls. CD33+/CD34+ cells from 22 patients with JMML showed hyperphosphorylation of STAT5 induced by sub-saturating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF). Using a training set of samples (11 JMML and 23 controls), we identified a threshold for p-STAT5-positive after stimulation with 0.1 ng/ml GM-CSF (17.17%) that discriminates JMML from controls. This threshold was validated in an independent series (11 JMML, 24 controls and 7 cases with diseases other than JMML) where we demonstrated that patients with JMML could be distinguished from other subjects with a sensitivity of 91% (confidence interval (CI) 59-100%) and a specificity of 87% (CI 70-96%). Positive and negative predictive values were 71% (CI 42-92%) and 96% (CI 82-100%), respectively. In conclusion, flow cytometric p-STAT5 profiling is a reliable diagnostic tool for identifying patients with JMML and can contribute to consistency of current diagnostic criteria.

Original languageEnglish
Article numbere160
JournalBlood Cancer Journal
Volume3
Issue number11
DOIs
Publication statusPublished - 2013

Keywords

  • GM-CSF
  • Juvenile myelomonocytic leukemia
  • Phospho-specific flow cytometry
  • Phospho-STAT5

ASJC Scopus subject areas

  • Oncology
  • Hematology

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    Hasegawa, D., Bugarin, C., Giordan, M., Bresolin, S., Longoni, D., Micalizzi, C., Ramenghi, U., Bertaina, A., Basso, G., Locatelli, F., Biondi, A., Kronnie, G. T., & Gaipa, G. (2013). Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia. Blood Cancer Journal, 3(11), [e160]. https://doi.org/10.1038/bcj.2013.56