The University of Southampton
University of Southampton Institutional Repository

EZH2 mutational status predicts poor survival in myelofibrosis

Guglielmelli, P., Biamonte, F., Score, J., Hidalgo-Curtis, C., Cervantes, F., Maffioli, M., Fanelli, T., Ernst, T., Winkelman, N., Jones, A. V., Zoi, K., Reiter, A., Duncombe, A., Villani, L., Bosi, A., Barosi, G., Cross, N. C. P. and Vannucchi, A. M. (2011) EZH2 mutational status predicts poor survival in myelofibrosis Blood, 118, (19), pp. 5227-5234. (doi:10.1182/blood-2011-06-363424).

Record type: Article

Abstract

We genotyped 370 subjects with primary myelofibrosis (PMF) and 148 with postpolycythemia vera/postessential thrombocythemia (PPV/PET) MF for mutations of EZH2. Mutational status at diagnosis was correlated with hematologic parameters, clinical manifestations, and outcome. A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF, and 9.4% of PET-MF patients; most were exonic heterozygous missense changes. EZH2 mutation coexisted with JAK2V617F or ASXL1 mutation in 12 of 29 (41.4%) and 6 of 27 (22.2%) evaluated patients; TET2 and CBL mutations were found in 2 and 1 patients, respectively. EZH2-mutated PMF patients had significantly higher leukocyte counts, blast-cell counts, and larger spleens at diagnosis, and most of them (52.6%) were in the high-risk International Prognostic Score System (IPSS) category. After a median follow-up of 39 months, 128 patients (25.9%) died, 81 (63.3%) because of leukemia. Leukemia-free survival (LFS) and overall survival (OS) were significantly reduced in EZH2-mutated PMF patients (P = .028 and P < .001, respectively); no such impact was seen for PPV/PET-MF patients, possibly due to the low number of mutated cases. In multivariate analysis, survival of PMF patients was predicted by IPSS high-risk category, a < 25% JAK2V617F allele burden, and EZH2 mutation status. We conclude that EZH2 mutations are independently associated with shorter survival in patients with PMF.

Full text not available from this repository.

More information

Accepted/In Press date: 14 September 2011
Published date: 10 November 2011
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 204063
URI: http://eprints.soton.ac.uk/id/eprint/204063
ISSN: 0006-4971
PURE UUID: d6635735-4771-4726-ba47-d8c833ba58b4
ORCID for N. C. P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

Catalogue record

Date deposited: 23 Nov 2011 12:05
Last modified: 18 Jul 2017 11:07

Export record

Altmetrics

Contributors

Author: P. Guglielmelli
Author: F. Biamonte
Author: J. Score
Author: C. Hidalgo-Curtis
Author: F. Cervantes
Author: M. Maffioli
Author: T. Fanelli
Author: T. Ernst
Author: N. Winkelman
Author: A. V. Jones
Author: K. Zoi
Author: A. Reiter
Author: A. Duncombe
Author: L. Villani
Author: A. Bosi
Author: G. Barosi
Author: N. C. P. Cross ORCID iD
Author: A. M. Vannucchi

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×