Molecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Magdalena M. Brune, Achim Rau, Mathis Overkamp, Tim Flaadt, Irina Bonzheim, Christian M. Schürch, Birgit Federmann, Stefan Dirnhofer, Falko Fend, Alexandar Tzankov
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	myeloproliferative neoplasm myelodysplastic/myeloproliferative neoplasm secondary acute myeloid leukemia genetic testing mutation analysis risk stratification Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e10c4ca1d79b43aa8a364a620f8f4d40
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e10c4ca1d79b43aa8a364a620f8f4d40
record_format	dspace
spelling	oai:doaj.org-article:e10c4ca1d79b43aa8a364a620f8f4d402021-11-25T17:01:17ZMolecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies10.3390/cancers132256052072-6694https://doaj.org/article/e10c4ca1d79b43aa8a364a620f8f4d402021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5605https://doaj.org/toc/2072-6694Myeloproliferative 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—apart from the initial driver mutations—that 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 (<i>ASXL1</i>, <i>DNMT3A</i>, <i>NRAS</i>, <i>SRSF2</i> and <i>TP53</i>) strongly correlated with progression and/or transformation, even if only one of these genes was mutated, and this particularly applied to MPN. <i>TET2</i> mutations were found to have a higher allelic frequency than the putative driver mutation in three progressing cases (“<i>TET2</i>-first”), whereas two stable cases displayed a <i>TET2</i>-positive subclone (“<i>TET2</i>-second”), 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.Magdalena M. BruneAchim RauMathis OverkampTim FlaadtIrina BonzheimChristian M. SchürchBirgit FedermannStefan DirnhoferFalko FendAlexandar TzankovMDPI AGarticlemyeloproliferative neoplasmmyelodysplastic/myeloproliferative neoplasmsecondary acute myeloid leukemiagenetic testingmutation analysisrisk stratificationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5605, p 5605 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myeloproliferative neoplasm myelodysplastic/myeloproliferative neoplasm secondary acute myeloid leukemia genetic testing mutation analysis risk stratification Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	myeloproliferative neoplasm myelodysplastic/myeloproliferative neoplasm secondary acute myeloid leukemia genetic testing mutation analysis risk stratification Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Magdalena M. Brune Achim Rau Mathis Overkamp Tim Flaadt Irina Bonzheim Christian M. Schürch Birgit Federmann Stefan Dirnhofer Falko Fend Alexandar Tzankov Molecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies
description	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—apart from the initial driver mutations—that 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 (<i>ASXL1</i>, <i>DNMT3A</i>, <i>NRAS</i>, <i>SRSF2</i> and <i>TP53</i>) strongly correlated with progression and/or transformation, even if only one of these genes was mutated, and this particularly applied to MPN. <i>TET2</i> mutations were found to have a higher allelic frequency than the putative driver mutation in three progressing cases (“<i>TET2</i>-first”), whereas two stable cases displayed a <i>TET2</i>-positive subclone (“<i>TET2</i>-second”), 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.
format	article
author	Magdalena M. Brune Achim Rau Mathis Overkamp Tim Flaadt Irina Bonzheim Christian M. Schürch Birgit Federmann Stefan Dirnhofer Falko Fend Alexandar Tzankov
author_facet	Magdalena M. Brune Achim Rau Mathis Overkamp Tim Flaadt Irina Bonzheim Christian M. Schürch Birgit Federmann Stefan Dirnhofer Falko Fend Alexandar Tzankov
author_sort	Magdalena M. Brune
title	Molecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies
title_short	Molecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies
title_full	Molecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies
title_fullStr	Molecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies
title_full_unstemmed	Molecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies
title_sort	molecular progression of myeloproliferative and myelodysplastic/myeloproliferative neoplasms: a study on sequential bone marrow biopsies
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e10c4ca1d79b43aa8a364a620f8f4d40
work_keys_str_mv	AT magdalenambrune molecularprogressionofmyeloproliferativeandmyelodysplasticmyeloproliferativeneoplasmsastudyonsequentialbonemarrowbiopsies AT achimrau molecularprogressionofmyeloproliferativeandmyelodysplasticmyeloproliferativeneoplasmsastudyonsequentialbonemarrowbiopsies AT mathisoverkamp molecularprogressionofmyeloproliferativeandmyelodysplasticmyeloproliferativeneoplasmsastudyonsequentialbonemarrowbiopsies AT timflaadt molecularprogressionofmyeloproliferativeandmyelodysplasticmyeloproliferativeneoplasmsastudyonsequentialbonemarrowbiopsies AT irinabonzheim molecularprogressionofmyeloproliferativeandmyelodysplasticmyeloproliferativeneoplasmsastudyonsequentialbonemarrowbiopsies AT christianmschurch molecularprogressionofmyeloproliferativeandmyelodysplasticmyeloproliferativeneoplasmsastudyonsequentialbonemarrowbiopsies AT birgitfedermann molecularprogressionofmyeloproliferativeandmyelodysplasticmyeloproliferativeneoplasmsastudyonsequentialbonemarrowbiopsies AT stefandirnhofer molecularprogressionofmyeloproliferativeandmyelodysplasticmyeloproliferativeneoplasmsastudyonsequentialbonemarrowbiopsies AT falkofend molecularprogressionofmyeloproliferativeandmyelodysplasticmyeloproliferativeneoplasmsastudyonsequentialbonemarrowbiopsies AT alexandartzankov molecularprogressionofmyeloproliferativeandmyelodysplasticmyeloproliferativeneoplasmsastudyonsequentialbonemarrowbiopsies
_version_	1718412808939372544

Molecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies

Ejemplares similares