title: Expression of pSTAT5 predicts FLT3 internal tandem duplications in acute myeloid leukemia.
abstract: Mutations of the Fms-like tyrosine kinase 3 (FLT3) can be detected in a significant number of acute myeloid leukemias (AML). Seventy-five cases of acute myeloid leukemia were evaluated for FLT3-internal tandem duplications (ITD) by polymerase chain reaction. Paraffin-embedded formalin-fixed trephine biopsies of these cases were evaluated for expression of phosphorylated signal transducer and activator of transcription 1 (pSTAT1), pSTAT3, and pSTAT5. Specific expression of pSTAT5 was proven in leukemic blasts in situ by double staining with a blast-specific marker. Expression of pSTAT5 in > or =1% of blasts was highly predictive of FLT3-ITD. Neither expression of pSTAT1 nor pSTAT3 were associated with FLT3 mutations. Altogether we conclude that pSTAT5 expression can precisely be assessed by immunohistochemistry in routinely processed bone marrow trephines, STAT5 is highly likely the preferred second messenger of FLT3-mediated signaling in AML, and expression of pSTAT5 is predictive of FLT3-ITD.
authors.affiliation: Institute of Pathology, University of Basel, Schönbeinstrasse 40, 4031 Basel, Switzerland.
authors.forename: Ellen Christina
authors.initials: EC
authors.lastname: Obermann
authors.forename: Caroline
authors.initials: C
authors.lastname: Arber
authors.forename: Martine
authors.initials: M
authors.lastname: Jotterand
authors.forename: Andre
authors.initials: A
authors.lastname: Tichelli
authors.forename: Petra
authors.initials: P
authors.lastname: Hirschmann
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001752:Blast Crisis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation / Q000235:genetics; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015290:Second Messenger Systems; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3