Activated STAT1 and STAT5 transcription factors in extramedullary hematopoietic tissue in a polycythemia vera patient carrying the JAK2 V617F mutation.
The somatic V617F mutation in the Janus kinase (JAK) 2 gene, which causes a valine to phenylalanine substitution at position 617, has recently been found in the majority of patients with polycythemia vera and in many cases with essential thrombocythemia or idiopathic myelofibrosis. Here, we report on a 76-year-old female patient presenting with JAK2V617F-positive polycythemia vera and a pelvic mass with extramedullary hematopoiesis. Immunohistochemistry demonstrated tyrosine phosphorylation of JAK2 kinase as well as STAT1 and STAT5 transcription factors. However, only a minority of the total STAT1 pool was tyrosine-phosphorylated and, in contrast to its unphosphorylated counterpart, phospho-STAT1 clearly showed nuclear accumulation. While megakaryotes expressed virtually no phospho-STAT1, phosphorylated STAT5 was mainly restricted to megakaryocytes and rarely detected in non-megakaryocytes. Our data suggest that dysregulated STAT signal pathways are engaged in extramedullary hematopoiesis in polycythemia vera.
Meyer
Thomas
T
Department of Cardiology, University of Marburg, Baldingerstrasse 1, 35033, Marburg, Germany. meyert@med.uni-marburg.de
Ruppert
Volker
V
Görg
Christian
C
Neubauer
Andreas
A
D000368:Aged; D005260:Female; D006411:Hematopoiesis, Extramedullary / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D053614:Janus Kinase 2 / Q000235:genetics*; D017354:Point Mutation; D011087:Polycythemia Vera / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D014463:Ultrasonography
D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2