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stem\/progenitor cells. The major clinical entities are represented by polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), that are caused by driver mutations affecting JAK2, MPL or CALR. Disease progression is related to molecular and clonal evolution. PV and ET can progress to secondary myelofibrosis (sMF) but can also evolve to secondary acute myeloid leukemia (sAML). PMF is associated with the highest frequency of leukemic transformation, which represents the main cause of death. sAML is associated with a dismal prognosis and clinical features that differ from those of de novo AML. The molecular landscape distinguishes sAML from de novo AML, since the most frequent hits involve TP53, epigenetic regulators, spliceosome modulators or signal transduction genes. Single cell genomic studies provide novel and accurate information about clonal architecture and mutation acquisition order, allowing the reconstruction of clonal dynamics and molecular events that accompany leukemic transformation. In this review, we examine our current understanding of the genomic heterogeneity in MPNs and how it affects disease progression and leukemic transformation. We focus on molecular events elicited by somatic mutations acquisition and discuss the emerging findings coming from single cell studies.<\/jats:p>","DOI":"10.3390\/ijms232315256","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T02:13:12Z","timestamp":1670206392000},"page":"15256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel Molecular Insights into Leukemic Evolution of Myeloproliferative Neoplasms: A Single Cell Perspective"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-4181","authenticated-orcid":false,"given":"Sebastiano","family":"Rontauroli","sequence":"first","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5952-0818","authenticated-orcid":false,"given":"Chiara","family":"Carretta","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, Life Sciences Department, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Parenti","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7896-5775","authenticated-orcid":false,"given":"Matteo","family":"Bertesi","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, Life Sciences Department, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0660-6110","authenticated-orcid":false,"given":"Rossella","family":"Manfredini","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 Revision to the World Health Organization Classification of Myeloid Neoplasms and Acute Leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating Morphologic, Clinical, and Genomic Data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1002\/ajh.26008","article-title":"Polycythemia Vera and Essential Thrombocythemia: 2021 Update on Diagnosis, Risk-stratification and Management","volume":"95","author":"Tefferi","year":"2020","journal-title":"Am. 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