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Rockefeller University Press, Journal of Experimental Medicine, 5(210), p. 1003-1019, 2013

DOI: 10.1084/jem.20120521

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

Journal article published in 2013 by Jonas S. Jutzi ORCID, Ruzhica Bogeska, Gorica Nikoloski, Corina A. Schmid, Thalia S. Seeger, Frank Stegelmann, Sven Schwemmers, Albert Gründer, Jan C. Peeken, Monika Gothwal, Julius Wehrle, Konrad Aumann, Kamar Hamdi, Christine Dierks, Wei Kamar Wang and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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.