{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:06:41Z","timestamp":1792033601071,"version":"4.4.0"},"reference-count":47,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swiss Life Jubil\u00e4umsstiftung","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Myeloproliferative neoplasms (MPN) and myelodysplastic\/myeloproliferative neoplasms (MDS\/MPN) both harbor the potential to undergo myelodysplastic progression or acceleration and can transform into blast-phase MPN or MDS\/MPN, a form of secondary acute myeloid leukemia (AML). Although the initiating transforming events are yet to be determined, current concepts suggest a stepwise acquisition of (additional) somatic mutations\u2014apart from the initial driver mutations\u2014that trigger disease evolution. In this study we molecularly analyzed paired bone marrow samples of MPN and MDS\/MPN patients with known progression and compared them to a control cohort of patients with stable disease course. Cases with progression displayed from the very beginning a higher number of mutations compared to stable ones, of which mutations in five (ASXL1, DNMT3A, NRAS, SRSF2 and TP53) strongly correlated with progression and\/or transformation, even if only one of these genes was mutated, and this particularly applied to MPN. TET2 mutations were found to have a higher allelic frequency than the putative driver mutation in three progressing cases (\u201cTET2-first\u201d), whereas two stable cases displayed a TET2-positive subclone (\u201cTET2-second\u201d), supporting the hypothesis that not only the sum of mutations but also their order of appearance matters in the course of disease. Our data emphasize the importance of genetic testing in MPN and MDS\/MPN patients in terms of risk stratification and identification of imminent disease progression.<\/jats:p>","DOI":"10.3390\/cancers13225605","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T12:46:23Z","timestamp":1636461983000},"page":"5605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular Progression of Myeloproliferative and Myelodysplastic\/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies"],"prefix":"10.3390","volume":"13","author":[{"given":"Magdalena M.","family":"Brune","sequence":"first","affiliation":[{"name":"Institute of Medical Genetics and Pathology, University Hospital Basel, Sch\u00f6nbeinstrasse 40, CH-4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-7038","authenticated-orcid":false,"given":"Achim","family":"Rau","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathis","family":"Overkamp","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2729-9941","authenticated-orcid":false,"given":"Tim","family":"Flaadt","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Bonzheim","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1792-1768","authenticated-orcid":false,"given":"Christian M.","family":"Sch\u00fcrch","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Institute of Pathology, University of Bern, Murtenstrasse 8, CH-3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Federmann","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Dirnhofer","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Pathology, University Hospital Basel, Sch\u00f6nbeinstrasse 40, CH-4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falko","family":"Fend","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1100-3819","authenticated-orcid":false,"given":"Alexandar","family":"Tzankov","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Pathology, University Hospital Basel, Sch\u00f6nbeinstrasse 40, CH-4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1080\/17474086.2020.1819232","article-title":"Co-Existence of Mutations in Myeloproliferative Neoplasms and Their Clinical Significance: A Prognostic Approach","volume":"13","author":"Pezeshki","year":"2020","journal-title":"Expert Rev. 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