{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:50:51Z","timestamp":1781877051125,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n Plasma cell myeloma is a heterogeneous hematologic malignancy characterized by clonal expansion of plasma cells. While RAS\u2010MAPK pathway mutations are known high\u2010risk features, the clinical relevance of\n STAT3<\/jats:italic>\n \/\n STAT5<\/jats:italic>\n mutations remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Method<\/jats:title>\n \n We analyzed 16 myeloma patients with\n STAT3<\/jats:italic>\n \/\n STAT5<\/jats:italic>\n mutations identified by next\u2010generation sequencing (9\n STAT3<\/jats:italic>\n , 5\n STAT5A<\/jats:italic>\n , 2\n STAT5B<\/jats:italic>\n ) and compared them with 32 mutation\u2010negative controls.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n STAT3<\/jats:italic>\n \/\n STAT5<\/jats:italic>\n mutations were present at initial diagnosis in all eight patients with available initial sequencing data, suggesting these are early events in pathogenesis.\n STAT3<\/jats:italic>\n \/\n STAT5<\/jats:italic>\n mutations were the sole mutations in five patients, while 10 had co\u2010mutations, most frequently in\n KRAS<\/jats:italic>\n \/\n NRAS<\/jats:italic>\n (\n n<\/jats:italic>\n \u2009=\u20095) and\n TP53<\/jats:italic>\n (\n n<\/jats:italic>\n \u2009=\u20093). In co\u2010mutated cases,\n STAT3<\/jats:italic>\n \/\n STAT5<\/jats:italic>\n represented the dominant clone in 4 and co\u2010dominant in 6. All mutations were missense, with 63% involving the SH2 domain. Compared with controls,\n STAT3<\/jats:italic>\n \/\n STAT5<\/jats:italic>\n \u2010mutated patients had higher serum lactate dehydrogenase levels, higher incidence of IgA paraprotein, higher R\u2010ISS stage, more complex karyotype, and frequent\n CKS1B<\/jats:italic>\n gain\/amplification. Overall survival was significantly shorter in patients with\n STAT3<\/jats:italic>\n \/\n STAT5<\/jats:italic>\n mutations (median 42 vs. 72\u2009months,\n p<\/jats:italic>\n \u2009<\u20090.0001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n STAT3<\/jats:italic>\n \/\n STAT5<\/jats:italic>\n mutations are early, dominant, and potentially pathogenic events in plasma cell myeloma. Their association with adverse clinical features and inferior survival supports their routine assessment and potential therapeutic targeting.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ejh.70174","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:50:21Z","timestamp":1775649021000},"page":"258-266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["STAT3<\/i>\n \/\n STAT5<\/i>\n Mutations Predict Shorter Overall Survival in Patients with Plasma Cell Myeloma"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1397-0968","authenticated-orcid":false,"given":"Matthew T.","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USA"},{"name":"Vanderbilt University School of Medicine Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steliana","family":"Calin","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaling","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. James","family":"You","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USA"},{"name":"Department of Pathology City of Hope National Medical Center Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"241","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th Edition)","author":"McKenna R. 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