{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:41:49Z","timestamp":1790804509771,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"Abstract<\/jats:title>\n \n We investigated using a custom NGS panel of 149 genes the mutational landscape of 64 consecutive adult patients with tyrosine kinase fusion\u2010negative hypereosinophilia (HE)\/hypereosinophilic syndrome (HES) harboring features suggestive of myeloid neoplasm. At least one mutation was reported in 50\/64 (78%) patients (compared to 8\/44 (18%) patients with idiopathic HE\/HES\/HE\n US<\/jats:sub>\n used as controls;\n p<\/jats:italic>\n \u2009<\u2009.001). Thirty\u2010five patients (54%) had at least one mutation involving the JAK\u2010STAT pathway, including\n STAT5B<\/jats:italic>\n (\n n<\/jats:italic>\n \u2009=\u200918, among which the hotspot N642H,\n n<\/jats:italic>\n \u2009=\u200913),\n JAK1<\/jats:italic>\n (indels in exon 13,\n n<\/jats:italic>\n \u2009=\u20095; V658F\/L,\n n<\/jats:italic>\n \u2009=\u20092), and\n JAK2<\/jats:italic>\n (V617F,\n n<\/jats:italic>\n \u2009=\u20096; indels in exon 13,\n n<\/jats:italic>\n \u2009=\u20092). Other previously undescribed somatic mutations were also found in\n JAK2<\/jats:italic>\n ,\n JAK1<\/jats:italic>\n ,\n STAT5B<\/jats:italic>\n , and\n STAT5A<\/jats:italic>\n , including three patients who shared the same\n STAT5A<\/jats:italic>\n V707fs mutation and features consistent with primary polycythemia. Nearly all JAK\u2010STAT mutations were preceded by (or associated with) myelodysplasia\u2010related gene mutations, especially in RNA\u2010splicing genes or chromatin modifiers. In multivariate analysis, neurologic involvement (hazard ratio [HR]\u00a04.95 [1.87\u201313.13];\n p<\/jats:italic>\n \u2009=\u2009.001), anemia (HR 5.50 [2.24\u201313.49];\n p<\/jats:italic>\n \u2009<\u2009.001), and the presence of a high\u2010risk mutation (as per the molecular international prognosis scoring system: HR 6.87 [2.39\u201319.72];\n p<\/jats:italic>\n \u2009<\u2009.001) were independently associated with impaired overall survival. While corticosteroids were ineffective in all treated JAK\u2010STAT\u2010mutated patients, ruxolitinib showed positive hematological responses including in\n STAT5A<\/jats:italic>\n \u2010mutated patients. These findings emphasize the usefulness of NGS for the workup of tyrosine kinase fusion\u2010negative HE\/HES patients and support the use of JAK inhibitors in this setting. Updated classifications could consider patients with JAK\u2010STAT mutations and eosinophilia as a new \u201cgene mutated\u2010entity\u201d that could be differentiated from CEL, NOS, and idiopathic HES.\n <\/jats:p>","DOI":"10.1002\/ajh.27306","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T09:24:57Z","timestamp":1712049897000},"page":"1108-1118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Involvement of the\n JAK<\/scp>\n \u2010\n STAT<\/scp>\n pathway in the molecular landscape of tyrosine kinase fusion\u2010negative hypereosinophilic syndromes: A nationwide\n CEREO<\/scp>\n study"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0810-136X","authenticated-orcid":false,"given":"Matthieu","family":"Groh","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, French National Reference Center for Hypereosinophilic 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