{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T17:33:05Z","timestamp":1785000785809,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The current study was inspired by observations from exploratory analyses of an institutional cohort with chronic myelomonocytic leukemia (CMML; <jats:italic>N<\/jats:italic>\u2009=\u2009398) that revealed no instances of blast transformation in the seven patients with plant homeodomain finger protein 6 (<jats:italic>PHF6<\/jats:italic>) mutation (<jats:italic>PHF6<\/jats:italic><jats:sup>MUT<\/jats:sup>). A subsequent Mayo Clinic enterprise\u2010wide database search identified 28 more cases with <jats:italic>PHF6<\/jats:italic><jats:sup>MUT<\/jats:sup>. Compared with their wild\u2010type <jats:italic>PHF6<\/jats:italic> counterparts (<jats:italic>PHF6<\/jats:italic><jats:sup>WT<\/jats:sup>; <jats:italic>N<\/jats:italic>\u2009=\u2009391), <jats:italic>PHF6<\/jats:italic><jats:sup>MUT<\/jats:sup> cases (<jats:italic>N<\/jats:italic>\u2009=\u200935) were more likely to co\u2010express <jats:italic>TET2<\/jats:italic> (89% vs. 45%; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01), <jats:italic>RUNX1<\/jats:italic> (29% vs. 14%; <jats:italic>p<\/jats:italic>\u2009=\u2009.03), <jats:italic>CBL<\/jats:italic> (14% vs. 2%; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01), and <jats:italic>U2AF1<\/jats:italic> (17% vs. 6%; <jats:italic>p<\/jats:italic>\u2009=\u2009.04) and less likely <jats:italic>SRSF2<\/jats:italic> (23% vs. 45%; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01) mutation. They were also more likely to display loss of Y chromosome (LoY; 21% vs. 2%; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01) and platelets &lt;100\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L (83% vs. 51%; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01). Multivariable analysis identified <jats:italic>PHF6<\/jats:italic><jats:sup>MUT<\/jats:sup> (HR 0.28, 95% CI 0.15\u20130.50) and <jats:italic>DNMT3A<\/jats:italic><jats:sup>MUT<\/jats:sup> (HR 5.8, 95% CI 3.3\u201310.5) as the strongest molecular predictors of overall survival. The same was true for blast transformation\u2010free survival with corresponding HR (95% CI) of 0.08 (0.01\u20130.6) and 9.5 (3.8\u201323.5). At median 20\u2009months follow\u2010up, blast transformation was documented in none of the 33 patients with <jats:italic>PHF6<\/jats:italic><jats:sup>MUT<\/jats:sup>\/<jats:italic>DNMT3A<\/jats:italic><jats:sup>WT<\/jats:sup> but in 6 (32%) of 19 with <jats:italic>DNMT3A<\/jats:italic><jats:sup>MUT<\/jats:sup> and 74 (20%) of 374 with <jats:italic>PHF6<\/jats:italic><jats:sup>WT<\/jats:sup>\/<jats:italic>DNMT3A<\/jats:italic><jats:sup>WT<\/jats:sup> (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01). The specific molecular signatures sustained their significant predictive performance in the context of the CMML\u2010specific molecular prognostic model (CPSS\u2010mol). <jats:italic>PHF6<\/jats:italic><jats:sup>MUT<\/jats:sup> identifies a unique subset of patients with CMML characterized by thrombocytopenia, higher prevalence of LoY, and superior prognosis.<\/jats:p>","DOI":"10.1002\/ajh.27492","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T12:18:49Z","timestamp":1727439529000},"page":"2321-2327","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<i>PHF6<\/i> mutations in chronic myelomonocytic leukemia identify a unique subset of patients with distinct phenotype and superior prognosis"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-3821","authenticated-orcid":false,"given":"Ayalew","family":"Tefferi","sequence":"first","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saubia","family":"Fathima","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Khalid A.","family":"Alsugair","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fnu","family":"Aperna","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota 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