{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:46:48Z","timestamp":1787957208398,"version":"build-2784847793"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mutations in cytokine receptor and JAK\/STAT; Cy\u2010JAK\/STAT) signaling genes drive myeloproliferative neoplasms (MPNs) but remain incompletely characterized in acute myeloid leukemia (AML). The authors evaluated the prevalence, clinical presentation, and prognostic significance of Cy\u2010JAK\/STAT pathway mutations in patients with AML and compared outcomes across disease ontogeny.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In total, 971 adults with newly diagnosed AML who were treated at the Cleveland Clinic between January 2015 and September 2023 were retrospectively analyzed. Baseline next\u2010generation sequencing was queried for eight Cy\u2010JAK\/STAT pathway genes:\n                      <jats:italic>CALR<\/jats:italic>\n                      ,\n                      <jats:italic>JAK1<\/jats:italic>\n                      ,\n                      <jats:italic>JAK2<\/jats:italic>\n                      ,\n                      <jats:italic>JAK3<\/jats:italic>\n                      ,\n                      <jats:italic>MPL<\/jats:italic>\n                      ,\n                      <jats:italic>SH2B3<\/jats:italic>\n                      ,\n                      <jats:italic>STAT3<\/jats:italic>\n                      , and\n                      <jats:italic>STAT5B<\/jats:italic>\n                      . Outcomes included composite\u2010complete remission (complete remission or complete remission with incomplete hematologic recovery), event\u2010free survival, and overall survival. In a prespecified subgroup of patients who had baseline molecular testing results available (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0621), those who had blast\u2010phase MPN (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a068), de novo AML with\n                      <jats:italic>JAK2<\/jats:italic>\n                      \/\n                      <jats:italic>CALR<\/jats:italic>\n                      \/\n                      <jats:italic>MPL<\/jats:italic>\n                      mutations (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a023), and de novo AML without Cy\u2010JAK\/STAT mutations (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0530) were compared.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mutation frequencies for the eight genes were as follows: JAK2, 43 of 625 patients (6.9%); CALR, nine of 623 (1.4%); SH2B3, eight of 392 (2.0%); JAK3, five of 439 (1.1%); MPL, one of 639 (0.2%); and STAT5B, one of 390 (0.3%); no JAK1 or STAT3 mutations were detected. The median follow\u2010up among survivors was 40.9 months, and the median overall survival was 12 months. JAK2\u2010mutated AML was associated with higher cardiovascular comorbidity, lower complete remission\/complete remission with incomplete hematologic recovery rates (32% vs. 54%), and inferior overall survival (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.05), but not on multivariable analysis. In subgroup analyses, patients who had blast\u2010phase MPN had the lowest response rate (13%) and the poorest survival; whereas patients who had de novo AML with\n                      <jats:italic>JAK2<\/jats:italic>\n                      ,\n                      <jats:italic>CALR<\/jats:italic>\n                      , or\n                      <jats:italic>MPL<\/jats:italic>\n                      mutations had intermediate outcomes versus those who had mutation\u2010negative, de novo AML (41% vs. 57% complete remission).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Cy\u2010JAK\/STAT pathway mutations are uncommon in AML, but each mutation has distinct biologic and clinical characteristics. The worse survival observed in patients with\n                      <jats:italic>JAK2<\/jats:italic>\n                      \u2010mutated AML largely appeared to be driven by the co\u2010occurrence of high\u2010risk characteristics. Blast\u2010phase MPN was associated with a dismal prognosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70465","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T06:06:15Z","timestamp":1779516375000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cytokine receptor and JAK\/STAT pathway mutations in acute myeloid leukemia: Prevalence and clinical impact"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1914-0054","authenticated-orcid":false,"given":"Moath","family":"Albliwi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Nurse","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Cleveland Clinic  Cleveland Ohio 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Version 2.2025. National Comprehensive Cancer Network;2025. 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