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Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia

Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia
Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia
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.
0887-6924
415-425
Cross, Nicholas
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Hoade, Yvette
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Tapper, William
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Carreno-Tarragona, Gonzalo
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Fanelli, Tiziana
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Jawhar, Mohamad
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Naumann, Nicole
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Pieniak, Iwo
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Lübke, Johannes
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Ali, Sahra
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Bhuller, Kaljit
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Burgstaller, Sonja
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Cargo, Catherine
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Cavenagh, Jamie
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Duncombe, Andrew S.
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Das-Gupta, Emma
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Evans, Paul
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Forsyth, Peter
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George, Philip
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Grimley, Charlotte
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Jack, Fergus
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Mehra, Varun
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Patel, Kavita
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Rismani, Ali
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Sciuccati, Gabriela
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Thomas-Dewing, Rowena
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Thornton, Patrick
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Virchis, Andres
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Watt, Simon
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Wallis, Louise
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Whiteway, Alistair
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Zegocki, Kris
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Bain, Barbara J.
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Reiter, Andreas
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Chase, Andrew
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Cross, Nicholas
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Hoade, Yvette
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Tapper, William
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Carreno-Tarragona, Gonzalo
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Fanelli, Tiziana
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Jawhar, Mohamad
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Naumann, Nicole
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Pieniak, Iwo
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Burgstaller, Sonja
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Cavenagh, Jamie
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Das-Gupta, Emma
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Evans, Paul
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Forsyth, Peter
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George, Philip
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Grimley, Charlotte
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Jack, Fergus
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Munro, Laura
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Mehra, Varun
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Rismani, Ali
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Sciuccati, Gabriela
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Thomas-Dewing, Rowena
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Thornton, Patrick
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Virchis, Andres
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Watt, Simon
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Wallis, Louise
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Whiteway, Alistair
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Zegocki, Kris
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Bain, Barbara J.
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Reiter, Andreas
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Chase, Andrew
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Cross, Nicholas, Hoade, Yvette, Tapper, William, Carreno-Tarragona, Gonzalo, Fanelli, Tiziana, Jawhar, Mohamad, Naumann, Nicole, Pieniak, Iwo, Lübke, Johannes, Ali, Sahra, Bhuller, Kaljit, Burgstaller, Sonja, Cargo, Catherine, Cavenagh, Jamie, Duncombe, Andrew S., Das-Gupta, Emma, Evans, Paul, Forsyth, Peter, George, Philip, Grimley, Charlotte, Jack, Fergus, Munro, Laura, Mehra, Varun, Patel, Kavita, Rismani, Ali, Sciuccati, Gabriela, Thomas-Dewing, Rowena, Thornton, Patrick, Virchis, Andres, Watt, Simon, Wallis, Louise, Whiteway, Alistair, Zegocki, Kris, Bain, Barbara J., Reiter, Andreas and Chase, Andrew (2019) Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia. Leukemia, 33 (2), 415-425. (doi:10.1038/s41375-018-0342-3).

Record type: Article

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.

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More information

Accepted/In Press date: 24 September 2018
e-pub ahead of print date: 20 December 2018
Published date: 1 February 2019

Identifiers

Local EPrints ID: 428194
URI: https://eprints.soton.ac.uk/id/eprint/428194
ISSN: 0887-6924
PURE UUID: 3815311d-f86b-4d28-a9d3-70494e5c9953
ORCID for Nicholas Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 14 Feb 2019 17:30
Last modified: 24 Mar 2019 05:01

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Contributors

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

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