MPN patients harbor recurrent truncating mutations in transcription factor NF-E2

作者：Jutzi Jonas S; Bogeska Ruzhica; Nikoloski Gorica; Schmid Corina A; Seeger Thalia S; Stegelmann Frank; Schwemmers Sven; Gruender Albert; Peeken Jan C; Gothwal Monika; Wehrle Julius; Aumann Konrad; Hamdi Kamar; Dierks Christine; Wang Wei; Doehner Konstanze; Jansen Joop H; Pahl Heike L^*

来源：Journal of Experimental Medicine, 2013, 210(5): 1003-1019.

DOI：10.1084/jem.20120521

The molecular etiology of myeloproliferative neoplasms (MPNs) remains incompletely understood, despite recent advances incurred through the discovery of several different mutations in MPN patients. We have recently described overexpression of the transcription factor NF-E2 in MPN patients and shown that elevated NF-E2 levels in vivo cause an MPN phenotype and predispose to leukemic transformation in transgenic mice. We report the presence of acquired insertion and deletion mutations in the NF-E2 gene in MPN patients. These result in truncated NF-E2 proteins that enhance wild-type (WT) NF-E2 function and cause erythrocytosis and thrombocytosis in a murine model. NF-E2 mutant cells acquire a proliferative advantage, witnessed by clonal dominance over WT NF-E2 cells in MPN patients. Our data underscore the role of increased NF-E2 activity in the pathophysiology of MPNs.

• 出版日期2013-5-6