Mutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis

Abstract Disease progression of myeloproliferative neoplasms is the result of increased genomic complexity. Since the ability to predict disease evolution is crucial for clinical decisions, we studied single-cell genomics and transcriptomics of CD34-positive cells from a primary myelofibrosis (PMF)...

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Autores principales:	Sandra Parenti, Sebastiano Rontauroli, Chiara Carretta, Selene Mallia, Elena Genovese, Chiara Chiereghin, Clelia Peano, Lara Tavernari, Elisa Bianchi, Sebastian Fantini, Stefano Sartini, Oriana Romano, Silvio Bicciato, Enrico Tagliafico, Matteo Della Porta, Rossella Manfredini
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/644d99d3c3d744418f3c13018b7b3bc7
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spelling	oai:doaj.org-article:644d99d3c3d744418f3c13018b7b3bc72021-12-02T14:40:00ZMutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis10.1038/s41698-021-00144-92397-768Xhttps://doaj.org/article/644d99d3c3d744418f3c13018b7b3bc72021-02-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00144-9https://doaj.org/toc/2397-768XAbstract Disease progression of myeloproliferative neoplasms is the result of increased genomic complexity. Since the ability to predict disease evolution is crucial for clinical decisions, we studied single-cell genomics and transcriptomics of CD34-positive cells from a primary myelofibrosis (PMF) patient who progressed to acute myeloid leukemia (AML) while receiving Ruxolitinib. Single-cell genomics allowed the reconstruction of clonal hierarchy and demonstrated that TET2 was the first mutated gene while FLT3 was the last one. Disease evolution was accompanied by increased clonal heterogeneity and mutational rate, but clones carrying TP53 and FLT3 mutations were already present in the chronic phase. Single-cell transcriptomics unraveled repression of interferon signaling suggesting an immunosuppressive effect exerted by Ruxolitinib. Moreover, AML transformation was associated with a differentiative block and immune escape. These results suggest that single-cell analysis can unmask tumor heterogeneity and provide meaningful insights about PMF progression that might guide personalized therapy.Sandra ParentiSebastiano RontauroliChiara CarrettaSelene MalliaElena GenoveseChiara ChiereghinClelia PeanoLara TavernariElisa BianchiSebastian FantiniStefano SartiniOriana RomanoSilvio BicciatoEnrico TagliaficoMatteo Della PortaRossella ManfrediniNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Sandra Parenti Sebastiano Rontauroli Chiara Carretta Selene Mallia Elena Genovese Chiara Chiereghin Clelia Peano Lara Tavernari Elisa Bianchi Sebastian Fantini Stefano Sartini Oriana Romano Silvio Bicciato Enrico Tagliafico Matteo Della Porta Rossella Manfredini Mutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis
description	Abstract Disease progression of myeloproliferative neoplasms is the result of increased genomic complexity. Since the ability to predict disease evolution is crucial for clinical decisions, we studied single-cell genomics and transcriptomics of CD34-positive cells from a primary myelofibrosis (PMF) patient who progressed to acute myeloid leukemia (AML) while receiving Ruxolitinib. Single-cell genomics allowed the reconstruction of clonal hierarchy and demonstrated that TET2 was the first mutated gene while FLT3 was the last one. Disease evolution was accompanied by increased clonal heterogeneity and mutational rate, but clones carrying TP53 and FLT3 mutations were already present in the chronic phase. Single-cell transcriptomics unraveled repression of interferon signaling suggesting an immunosuppressive effect exerted by Ruxolitinib. Moreover, AML transformation was associated with a differentiative block and immune escape. These results suggest that single-cell analysis can unmask tumor heterogeneity and provide meaningful insights about PMF progression that might guide personalized therapy.
format	article
author	Sandra Parenti Sebastiano Rontauroli Chiara Carretta Selene Mallia Elena Genovese Chiara Chiereghin Clelia Peano Lara Tavernari Elisa Bianchi Sebastian Fantini Stefano Sartini Oriana Romano Silvio Bicciato Enrico Tagliafico Matteo Della Porta Rossella Manfredini
author_facet	Sandra Parenti Sebastiano Rontauroli Chiara Carretta Selene Mallia Elena Genovese Chiara Chiereghin Clelia Peano Lara Tavernari Elisa Bianchi Sebastian Fantini Stefano Sartini Oriana Romano Silvio Bicciato Enrico Tagliafico Matteo Della Porta Rossella Manfredini
author_sort	Sandra Parenti
title	Mutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis
title_short	Mutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis
title_full	Mutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis
title_fullStr	Mutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis
title_full_unstemmed	Mutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis
title_sort	mutated clones driving leukemic transformation are already detectable at the single-cell level in cd34-positive cells in the chronic phase of primary myelofibrosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/644d99d3c3d744418f3c13018b7b3bc7
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Mutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis

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