STAT1 activation in association with JAK2 exon 12 mutations

JAK2 exon 12 mutations are associated with more marked and isolated erythrocytosis than JAK2V617F. We analyzed expression profiles of JAK2 exon 12-mutant and wild-type erythroid colonies from patients with poly- cythemia vera (PV). Exon 12 mutations were associated with interferon-target gene upregulation, STAT1 activa- tion and additional gene expression changes that were quantitatively and qualitatively similar to those in JAK2V617F-heterozygous cells from essential thrombo- cythemia (ET) patients. These results demonstrate that JAK2 exon 12-mutated PV does not reflect attenuated STAT1 signaling, and that transcriptional consequences of JAK2 mutations are remarkably similar in JAK2 exon 12-mutated PV and JAK2V617F-positive ET.