Distinct Clinical Phenotypes Associated with JAK2V617F Reflect Differential STAT1 Signaling

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2010 Nov 16

PMID 21074499

Citations 79

Authors

Edwin Chen

Philip A Beer

Anna L Godfrey

Christina A Ortmann

Juan Li

Ana P Costa-Pereira

Catherine E Ingle

Emmanouil T Dermitzakis

Peter J Campbell

Anthony R Green

Affiliations

Soon will be listed here.

Abstract

The JAK2V617F 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.

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