{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:11:05Z","timestamp":1760148665955,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are two of the main BCR-ABL1-negative chronic myeloproliferative neoplasms (MPNs) characterized by abnormal megakaryocytic proliferation. Janus kinase 2 (JAK2) mutations are detected in 50\u201360% of ET and PMF, while myeloproliferative leukemia (MPL) virus oncogene mutations are present in 3\u20135% of cases. While Sanger sequencing is a valuable diagnostic tool to discriminate the most common MPN mutations, next-generation sequencing (NGS) is a more sensitive technology that also identifies concurrent genetic alterations. In this report, we describe two MPN patients with simultaneous double MPL mutations: a woman with ET presenting both MPLV501A-W515R and JAK2V617F mutations and a man with PMF displaying an uncommon double MPLV501A-W515L. Using colony-forming assays and NGS analyses, we define the origin and mutational landscape of these two unusual malignancies and uncover further gene alterations that may contribute to the pathogenesis of ET and PMF.<\/jats:p>","DOI":"10.3390\/hematolrep15020033","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T08:14:28Z","timestamp":1684829668000},"page":"317-324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Additional Genetic Alterations and Clonal Evolution of MPNs with Double Mutations on the MPL Gene: Two Case Reports"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4442-4406","authenticated-orcid":false,"given":"Maria Stella","family":"Pennisi","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Di Gregorio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8012-5134","authenticated-orcid":false,"given":"Elena","family":"Tirr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-8266","authenticated-orcid":false,"given":"Chiara","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-4755","authenticated-orcid":false,"given":"Andrea","family":"Duminuco","sequence":"additional","affiliation":[{"name":"Postgraduate School of Hematology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7540-805X","authenticated-orcid":false,"given":"Bruno","family":"Garibaldi","sequence":"additional","affiliation":[{"name":"Postgraduate School of Hematology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaetano","family":"Giuffrida","sequence":"additional","affiliation":[{"name":"Hematology Unit and Bone Marrow Transplant, A.O.U. Policlinico \u201cG. Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia","family":"Manzella","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5943-6066","authenticated-orcid":false,"given":"Paolo","family":"Vigneri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-6319","authenticated-orcid":false,"given":"Giuseppe A.","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical Sciences and Advanced Technologies, \u201cG.F. Ingrassia\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3389\/fonc.2019.00321","article-title":"The Role of New Technologies in Myeloproliferative Neoplasms","volume":"9","author":"Palumbo","year":"2019","journal-title":"Front. 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