Novel Molecular Insights into Leukemic Evolution of Myeloproliferative Neoplasms: A Single Cell Perspective
Myeloproliferative neoplasms (MPNs) are clonal disorders originated by the serial acquisition of somatic mutations in hematopoietic stem/progenitor cells. The major clinical entities are represented by polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), that are...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15256 |
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| author | Sebastiano Rontauroli Chiara Carretta Sandra Parenti Matteo Bertesi Rossella Manfredini |
| author_facet | Sebastiano Rontauroli Chiara Carretta Sandra Parenti Matteo Bertesi Rossella Manfredini |
| author_sort | Sebastiano Rontauroli |
| collection | DOAJ |
| description | Myeloproliferative neoplasms (MPNs) are clonal disorders originated by the serial acquisition of somatic mutations in hematopoietic 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 <i>JAK2</i>, <i>MPL</i> or <i>CALR</i>. 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 <i>TP53</i>, 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. |
| first_indexed | 2024-03-09T17:44:45Z |
| format | Article |
| id | doaj.art-a2b919ed35024a559f3aa43d9dad5a17 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:45Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a2b919ed35024a559f3aa43d9dad5a172023-11-24T11:15:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231525610.3390/ijms232315256Novel Molecular Insights into Leukemic Evolution of Myeloproliferative Neoplasms: A Single Cell PerspectiveSebastiano Rontauroli0Chiara Carretta1Sandra Parenti2Matteo Bertesi3Rossella Manfredini4Centre for Regenerative Medicine “Stefano Ferrari”, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyCentre for Regenerative Medicine “Stefano Ferrari”, Life Sciences Department, University of Modena and Reggio Emilia, 41125 Modena, ItalyCentre for Regenerative Medicine “Stefano Ferrari”, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyCentre for Regenerative Medicine “Stefano Ferrari”, Life Sciences Department, University of Modena and Reggio Emilia, 41125 Modena, ItalyCentre for Regenerative Medicine “Stefano Ferrari”, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyMyeloproliferative neoplasms (MPNs) are clonal disorders originated by the serial acquisition of somatic mutations in hematopoietic 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 <i>JAK2</i>, <i>MPL</i> or <i>CALR</i>. 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 <i>TP53</i>, 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.https://www.mdpi.com/1422-0067/23/23/15256molecular pathogenesismolecular landscapesingle cell genomicssingle cell transcriptomics myeloproliferative neoplasmsleukemic transformation |
| spellingShingle | Sebastiano Rontauroli Chiara Carretta Sandra Parenti Matteo Bertesi Rossella Manfredini Novel Molecular Insights into Leukemic Evolution of Myeloproliferative Neoplasms: A Single Cell Perspective International Journal of Molecular Sciences molecular pathogenesis molecular landscape single cell genomics single cell transcriptomics myeloproliferative neoplasms leukemic transformation |
| title | Novel Molecular Insights into Leukemic Evolution of Myeloproliferative Neoplasms: A Single Cell Perspective |
| title_full | Novel Molecular Insights into Leukemic Evolution of Myeloproliferative Neoplasms: A Single Cell Perspective |
| title_fullStr | Novel Molecular Insights into Leukemic Evolution of Myeloproliferative Neoplasms: A Single Cell Perspective |
| title_full_unstemmed | Novel Molecular Insights into Leukemic Evolution of Myeloproliferative Neoplasms: A Single Cell Perspective |
| title_short | Novel Molecular Insights into Leukemic Evolution of Myeloproliferative Neoplasms: A Single Cell Perspective |
| title_sort | novel molecular insights into leukemic evolution of myeloproliferative neoplasms a single cell perspective |
| topic | molecular pathogenesis molecular landscape single cell genomics single cell transcriptomics myeloproliferative neoplasms leukemic transformation |
| url | https://www.mdpi.com/1422-0067/23/23/15256 |
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