Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12-20

AUTHORS

Nicholas C. P. Cross, Yvette Hoade, William J. Tapper, Gonzalo Carreno-Tarragona, Tiziana Fanelli, Mohamad Jawhar, Nicole Naumann, Iwo Pieniak, Johannes Lübke, Sahra Ali, Kaljit Bhuller, Sonja Burgstaller, Catherine Cargo, Jamie Cavenagh, Andrew S. Duncombe, Emma Das-Gupta, Paul Evans, Peter Forsyth, Philip George, Charlotte Grimley, Fergus Jack, Laura Munro, Varun Mehra, Kavita Patel, Ali Rismani, Gabriela Sciuccati, Rowena Thomas-Dewing, Patrick Thornton, Andres Virchis, Simon Watt, Louise Wallis, Alastair Whiteway, Kris Zegocki, Barbara J. Bain, Andreas Reiter, Andrew Chase

ABSTRACT

Determining the underlying cause of persistent eosinophilia is important for effective clinical management but remains a diagnostic challenge in many cases. We identified STAT5B N642H, an established oncogenic mutation, in 27/1715 (1.6%) cases referred for investigation of eosinophilia. Of the 27 mutated cases, a working diagnosis of hypereosinophilic syndrome (HES; n = 7) or a myeloid neoplasm with eosinophilia (n = 20) had been made prior to the detection of STAT5B N642H. Myeloid panel analysis identified a median of 2 additional mutated genes (range 0-4) with 4 cases having STAT5B N642H as a sole abnormality. STAT5B N642H was absent in cultured T cells of 4/4 positive cases. Individuals with SF3B1 mutations (9/27; 33%) or STAT5B N642H as a sole abnormality had a markedly better overall survival compared to cases with other additional mutations (median 65 months vs. 14 months; hazard ratio = 8.1; P < 0.001). The overall survival of STAT5B-mutated HES cases was only 30 months, suggesting that these cases should be reclassified as chronic eosinophilic leukemia, not otherwise specified (CEL-NOS). The finding of STAT5B N642H as a recurrent mutation in myeloid neoplasia with eosinophilia provides a new diagnostic and prognostic marker as well as a potential target for therapy. More... »

PAGES

1-11

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41375-018-0342-3

DOI

http://dx.doi.org/10.1038/s41375-018-0342-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110814572

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30573779


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487 https://www.grid.ac/institutes/grid.443984.6 schema:alternateName St James's University Hospital
488 schema:name HMDS, St. James’s University Hospital, Leeds, UK
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490 https://www.grid.ac/institutes/grid.459707.8 schema:alternateName Klinikum Wels-Grieskirchen
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499 https://www.grid.ac/institutes/grid.5491.9 schema:alternateName University of Southampton
500 schema:name Faculty of Medicine, University of Southampton, Southampton, UK
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