Author/Authors :
Chen، نويسنده , , Edwin and Beer، نويسنده , , Philip A. and Godfrey، نويسنده , , Anna L. and Ortmann، نويسنده , , Christina A. and Li، نويسنده , , Juan and Costa-Pereira، نويسنده , , Ana P. and Ingle، نويسنده , , Catherine E. and Dermitzakis، نويسنده , , Emmanouil T. and Campbell، نويسنده , , Peter J. and Green، نويسنده , , Anthony R.، نويسنده ,
Abstract :
Summary
K2V617F mutation is associated with distinct myeloproliferative neoplasms, including polycythemia vera (PV) and essential thrombocythemia (ET), but it remains unclear how it generates disparate disorders. By comparing clonally-derived mutant and wild-type cells from individual patients, we demonstrate that the transcriptional consequences of JAK2V617F are subtle, and that JAK2V617F-heterozygous erythroid cells from ET and PV patients exhibit differential interferon signaling and STAT1 phosphorylation. Increased STAT1 activity in normal CD34-positive progenitors produces an ET-like phenotype, whereas downregulation of STAT1 activity in JAK2V617F-heterozygous ET progenitors produces a PV-like phenotype. Our results illustrate the power of clonal analysis, indicate that the consequences of JAK2V617F reflect a balance between STAT5 and STAT1 activation and are relevant for other neoplasms associated with signaling pathway mutations.
