{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:40:26Z","timestamp":1792813226259,"version":"4.5.0"},"reference-count":62,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,2]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Secondary myelofibrosis (SMF) represents a late stage of polycythemia vera (PV) and essential thrombocythemia (ET), with overall survival (OS) currently defined by the myelofibrosis secondary to PV and ET prognostic model (MYSEC-PM). To identify additional myeloid neoplasm\u2013associated cancer gene variants (CGVs) associated with SMF outcome, we evaluated next-generation sequencing panel testing in 644 patients within the MYSEC cohort. Overall, 429 (66.6%) patients reported at least 1 CGV, with ASXL1, TET2, and DNMT3A being the most frequently involved. Specific molecular profiles affected OS (P&amp;lt; .001): U2AF1, TP53, or SRSF2 variants (UTS; 9.3%; median OS, 4.1 years) and ASXL1 without UTS (25.3%; median OS, 8.4 years). By integrating these genetic signatures within the MYSEC-PM through penalized Cox regressions, we identified the following independent predictors (P&amp;lt; .0001 to .02): hemoglobin level &amp;lt;11 g\/dL (1 point), circulating blasts \u22653% (2 points), platelet count &amp;lt;150 \u00d7 109\/L (2 points), age (0.21 points\/y), ASXL1 without UTS mutations (1 point), and any UTS mutations (3 points). Finally, we developed the MYSEC-molecular prognostic model (MYSEC-mPM) allocating 582 patients with SMF into 4 categories with different OS (P &amp;lt; .001): low (median OS, 18.0 years; score &amp;lt;14), intermediate-1 (8.8. years; score, 14-16), intermediate-2 (4.6 years; score, 17-18), and high risk (1.9 years; score \u226519). Additionally, in 381 patients with SMF and available cytogenetics, the MYSEC-mPM was implemented with complex\/monosomal karyotype, generating the karyotype-enhanced MYSEC-kmPM. Our study shows that genomic and cytogenetic profiling improves survival prediction in SMF, outperforming the MYSEC-PM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025031366","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T19:02:57Z","timestamp":1772737377000},"page":"43-57","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Genomic profiling for decision-making in post\u2013polycythemia vera and post\u2013essential thrombocythemia myelofibrosis"],"prefix":"10.1182","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6325-3916","authenticated-orcid":false,"given":"Barbara","family":"Mora","sequence":"first","affiliation":[{"name":"1Hematology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8367-5668","authenticated-orcid":false,"given":"Francesca","family":"Palandri","sequence":"additional","affiliation":[{"name":"2Seragnoli Hematology Institute, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1809-284X","authenticated-orcid":false,"given":"Paola","family":"Guglielmelli","sequence":"additional","affiliation":[{"name":"3Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9040-7415","authenticated-orcid":false,"given":"Andrew T.","family":"Kuykendall","sequence":"additional","affiliation":[{"name":"4Malignant Hematology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2268-391X","authenticated-orcid":false,"given":"Margherita","family":"Maffioli","sequence":"additional","affiliation":[{"name":"5Hematology, ASST Sette Laghi, Ospedale di Circolo, Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-0812","authenticated-orcid":false,"given":"Alessandra","family":"Iurlo","sequence":"additional","affiliation":[{"name":"1Hematology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5178-5827","authenticated-orcid":false,"given":"Valerio","family":"De Stefano","sequence":"additional","affiliation":[{"name":"6Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University, Fondazione Policlinico Gemelli IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Salmoiraghi","sequence":"additional","affiliation":[{"name":"7FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6881-417X","authenticated-orcid":false,"given":"Timothy","family":"Devos","sequence":"additional","affiliation":[{"name":"8Department of Hematology, University Hospitals Leuven and Department of Microbiology and Immunology, Laboratory of Molecular Immunology (Rega Institute), KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3532-5281","authenticated-orcid":false,"given":"Federico","family":"Itri","sequence":"additional","affiliation":[{"name":"9SCDU Internal Medicine with Haematological Focus, Onco-Haematological DH, AOU San Luigi Gonzaga, Orbassano, 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