Detection of phospho-STAT5 in mast cells: a reliable phenotypic marker of systemic mast cell disease that reflects constitutive tyrosine kinase activation.

Abstract	Systemic mastocytosis (SM) is characterized by the abnormal proliferation and accumulation of mast cells (MCs). Constitutive activation of kit, a receptor tyrosine kinase (TK), has been associated with all types of SM. Signal transducers and activators of transcription (STATs), such as STAT5, mediate downstream kit signalling. We hypothesized that nuclear phospho-STAT5 (pSTAT5) in MCs might reflect TK activation and would be a marker of abnormal MCs in SM. Expression of tryptase, CD25, CD2 and pSTAT5 was evaluated by immunohistochemistry (IHC) on archival cases of SM and cutaneous mastocytosis (CM). pSTAT5 was detected in 23/23 of SM and 1/9 of CM MC nuclei. 23/23 SM had CD25 + MCs. Control tissue MCs were negative for pSTAT5. Nuclear pSTAT5 in MCs from SM reflects abnormal TK activation. We propose nuclear pSTAT5 positivity in MCs as an additional minor phenotypic criterion for diagnosis of SM in future World Health Organization classification schemes.
Authors	Tania Zuluaga Toro, Fred H Hsieh, Juraj Bodo, Henry Y Dong, Eric D Hsi
Journal	British journal of haematology (Br J Haematol) Vol. 139 Issue 1 Pg. 31-40 (Oct 2007) ISSN: 0007-1048 [Print] England
PMID	17662084 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Biomarkers CD2 Antigens Interleukin-2 Receptor alpha Subunit STAT5 Transcription Factor Stem Cell Factor Protein-Tyrosine Kinases Tryptases
Topics	Adolescent Adult Aged Base Sequence Biomarkers (analysis) Bone Marrow Examination CD2 Antigens (analysis) Cell Nucleus (chemistry) Child Child, Preschool Female Flow Cytometry Humans Immunohistochemistry Infant Infant, Newborn Interleukin-2 Receptor alpha Subunit (analysis) Male Mast Cells (chemistry, metabolism) Mastocytosis, Cutaneous (enzymology) Mastocytosis, Systemic (diagnosis, enzymology) Middle Aged Molecular Sequence Data Mutation Protein-Tyrosine Kinases (metabolism) STAT5 Transcription Factor (analysis, genetics) Sequence Alignment Stem Cell Factor (genetics) Tryptases (analysis)

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