Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia

被引：79

作者：

Cross, Nicholas C. P. ^{[1
,2
]}

Hoade, Yvette ^{[1
,2
]}

Tapper, William J. ^{[1
]}

Carreno-Tarragona, Gonzalo ^{[1
,2
]}

Fanelli, Tiziana ^{[3
]}

Jawhar, Mohamad ^{[4
]}

Naumann, Nicole ^{[4
]}

Pieniak, Iwo ^{[1
]}

Luebke, Johannes ^{[4
]}

Ali, Sahra ^{[5
]}

Bhuller, Kaljit ^{[6
]}

Burgstaller, Sonja ^{[7
]}

Cargo, Catherine ^{[8
]}

Cavenagh, Jamie ^{[9
]}

Duncombe, Andrew S. ^{[10
]}

Das-Gupta, Emma ^{[11
]}

Evans, Paul ^{[8
]}

Forsyth, Peter ^{[12
]}

George, Philip ^{[11
]}

Grimley, Charlotte ^{[11
]}

Jack, Fergus ^{[13
]}

Munro, Laura ^{[14
]}

Mehra, Varun ^{[15
]}

Patel, Kavita ^{[16
]}

Rismani, Ali ^{[17
]}

Sciuccati, Gabriela ^{[18
]}

Thomas-Dewing, Rowena ^{[19
]}

Thornton, Patrick ^{[20
]}

Virchis, Andres ^{[21
]}

Watt, Simon ^{[22
]}

Wallis, Louise ^{[23
]}

Whiteway, Alastair ^{[24
]}

Zegocki, Kris ^{[25
]}

Bain, Barbara J. ^{[26
]}

Reiter, Andreas ^{[4
]}

Chase, Andrew ^{[1
,2
]}

机构：

[1] Univ Southampton, Fac Med, Southampton, Hants, England

[2] Salisbury NHS Fdn Trust, Wessex Reg Genet Lab, Salisbury, Wilts, England

[3] Univ Florence, AOU Careggi, Ctr Res & Innovat Myeloproliferat Neoplasms, Florence, Italy

[4] Heidelberg Univ, Univ Hosp Mannheim, Mannheim, Germany

[5] Hull & East Yorkshire Hosp NHS Trust, Kingston Upon Hull, N Humberside, England

[6] Univ Hosp Leicester NHS Trust, Leicester, Leics, England

[7] Klinikum Wels Grieskirchen, Wels, Austria

[8] St James Univ Hosp, HMDS, Leeds, W Yorkshire, England

[9] St Bartholomews Hosp, London, England

[10] Univ Hosp Southampton, Southampton, Hants, England

[11] Nottingham Univ Hosp NHS Trust, Nottingham, England

[12] Raigmore Hosp, Inverness, Scotland

[13] Poole Hosp NHS Trust, Poole, Dorset, England

[14] York Teaching Hosp NHS Trust, York, N Yorkshire, England

[15] Kings Coll Hosp London, London, England

[16] Mid Yorkshire Hosp NHS Trust, Wakefield, England

[17] Whittington Hlth & Univ Coll London Hosp, London, England

[18] Hosp Pediat Prof Dr Garrahan, Buenos Aires, DF, Argentina

[19] Salford Royal Hosp, Salford, Lancs, England

[20] Beaumont & Connolly Hosp, Dublin, Ireland

[21] Barnet Hosp, Royal Free London, Wellhouse Lane, Barnet, England

[22] Manchester Univ NHS FT, Manchester, Lancs, England

[23] Royal Bournemouth Hosp, Bournemouth, Dorset, England

[24] Southmead Hosp, Bristol, Avon, England

[25] Whipps Cross Univ Hosp, London, England

[26] St Marys Hosp, London, England

来源：

LEUKEMIA | 2019年 / 33卷 / 02期

关键词：

MYELOID/LYMPHOID NEOPLASMS; HYPEREOSINOPHILIC SYNDROME; LEUKEMIA; PDGFRB; SUBSET; RISK;

D O I：

10.1038/s41375-018-0342-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：415 / 425

页数：11

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