Different STAT-3 and STAT-5 phosphorylation discriminates among Ph-negative chronic myeloproliferative diseases and is independent of the V617F JAK-2 mutation.
The V617F JAK2 mutation reported in Ph-negative myeloproliferative diseases (MPDs) induces the constitutive activation of JAK2, which produces an increased phosphorylation of signal transducer activator of transcription (STAT). In this study, we have analyzed a series of 114 patients (54 with polycythemia vera [PV], 44 with essential thrombocythemia [ET], 12 with idiopathic myelofibrosis [IM], and 4 with myelofibrosis secondary to MPD) for the expression pattern of phosphorylated STAT-3 and STAT-5 (pSTAT-3 and pSTAT-5, respectively) by immunostaining bone marrow biopsies. We found 3 specific patterns of pSTAT-3 and pSTAT-5 expression, significantly different from the normal staining pattern: uniformly increased pSTAT-3 and pSTAT-5 expression in PV, increased pSTAT-3 and reduced pSTAT-5 expression in ET, and uniformly reduced pSTAT-3 and pSTAT-5 expression in IM. A moderate increase of pSTAT-3 and pSTAT-5 expression was observed in secondary forms of erythrocytosis and thrombocytosis. In all evaluated MPDs, the pSTAT-5 and pSTAT-3 expression pattern was not influenced by the presence of V617F JAK2 mutation. These findings underline the importance of bone marrow histology in the differential diagnosis of Ph-negative MPD and support the hypothesis that V617F mutation simply contributes with other molecular defects in allowing the PV, ET, or IM phenotype to emerge.
Teofili
Luciana
L
Departments of Hematology, Catholic University of Rome, Italy.
Martini
Maurizio
M
Cenci
Tonia
T
Petrucci
Giovanna
G
Torti
Lorenza
L
Storti
Sergio
S
Guidi
Francesco
F
Leone
Giuseppe
G
Larocca
Luigi Maria
LM
D001856:Bone Marrow Examination; D003937:Diagnosis, Differential; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000175:diagnosis*; D010677:Philadelphia Chromosome; D010766:Phosphorylation; D017354:Point Mutation; D011087:Polycythemia Vera / Q000175:diagnosis; D055728:Primary Myelofibrosis / Q000175:diagnosis; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000032:analysis / Q000378:metabolism*; D013920:Thrombocythemia, Essential / Q000175:diagnosis
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D053614:Janus Kinase 2