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Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes
Acute myeloid leukemias (AML) with myelodysplasia-related changes (AML-MRC) are defined by the presence of multilineage dysplasia (MLD), and/or myelodysplastic syndrome (MDS)-related cytogenetics, and/or previous MDS. The goal of this study was to identify distinct biological and prognostic subgroup...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480760/ https://www.ncbi.nlm.nih.gov/pubmed/25860933 |
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author | Devillier, Raynier Mansat-De Mas, Véronique Gelsi-Boyer, Veronique Demur, Cecile Murati, Anne Corre, Jill Prebet, Thomas Bertoli, Sarah Brecqueville, Mandy Arnoulet, Christine Recher, Christian Vey, Norbert Mozziconacci, Marie-Joelle Delabesse, Eric Birnbaum, Daniel |
author_facet | Devillier, Raynier Mansat-De Mas, Véronique Gelsi-Boyer, Veronique Demur, Cecile Murati, Anne Corre, Jill Prebet, Thomas Bertoli, Sarah Brecqueville, Mandy Arnoulet, Christine Recher, Christian Vey, Norbert Mozziconacci, Marie-Joelle Delabesse, Eric Birnbaum, Daniel |
author_sort | Devillier, Raynier |
collection | PubMed |
description | Acute myeloid leukemias (AML) with myelodysplasia-related changes (AML-MRC) are defined by the presence of multilineage dysplasia (MLD), and/or myelodysplastic syndrome (MDS)-related cytogenetics, and/or previous MDS. The goal of this study was to identify distinct biological and prognostic subgroups based on mutations of ASXL1, RUNX1, DNMT3A, NPM1, FLT3 and TP53 in 125 AML-MRC patients according to the presence of MLD, cytogenetics and outcome. ASXL1 mutations (n=26, 21%) were associated with a higher proportion of marrow dysgranulopoiesis (mutant vs. wild-type: 75% vs. 55%, p=0.030) and were mostly found in intermediate cytogenetic AML (23/26) in which they predicted inferior 2-year overall survival (OS, mutant vs. wild-type: 14% vs. 37%, p=0.030). TP53 mutations (n=28, 22%) were mostly found in complex karyotype AML (26/28) and predicted poor outcome within unfavorable cytogenetic risk AML (mutant vs. wild-type: 9% vs. 40%, p=0.040). In multivariate analysis, the presence of either ASXL1 or TP53 mutation was the only independent factor associated with shorter OS (HR, 95%CI: 2.53, 1.40-4.60, p=0.002) while MLD, MDS-related cytogenetics and previous MDS history did not influence OS. We conclude that ASXL1 and TP53 mutations identify two molecular subgroups among AML-MRCs, with specific poor prognosis. This could be useful for future diagnostic and prognostic classifications. |
format | Online Article Text |
id | pubmed-4480760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-44807602015-06-26 Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes Devillier, Raynier Mansat-De Mas, Véronique Gelsi-Boyer, Veronique Demur, Cecile Murati, Anne Corre, Jill Prebet, Thomas Bertoli, Sarah Brecqueville, Mandy Arnoulet, Christine Recher, Christian Vey, Norbert Mozziconacci, Marie-Joelle Delabesse, Eric Birnbaum, Daniel Oncotarget Clinical Research Paper Acute myeloid leukemias (AML) with myelodysplasia-related changes (AML-MRC) are defined by the presence of multilineage dysplasia (MLD), and/or myelodysplastic syndrome (MDS)-related cytogenetics, and/or previous MDS. The goal of this study was to identify distinct biological and prognostic subgroups based on mutations of ASXL1, RUNX1, DNMT3A, NPM1, FLT3 and TP53 in 125 AML-MRC patients according to the presence of MLD, cytogenetics and outcome. ASXL1 mutations (n=26, 21%) were associated with a higher proportion of marrow dysgranulopoiesis (mutant vs. wild-type: 75% vs. 55%, p=0.030) and were mostly found in intermediate cytogenetic AML (23/26) in which they predicted inferior 2-year overall survival (OS, mutant vs. wild-type: 14% vs. 37%, p=0.030). TP53 mutations (n=28, 22%) were mostly found in complex karyotype AML (26/28) and predicted poor outcome within unfavorable cytogenetic risk AML (mutant vs. wild-type: 9% vs. 40%, p=0.040). In multivariate analysis, the presence of either ASXL1 or TP53 mutation was the only independent factor associated with shorter OS (HR, 95%CI: 2.53, 1.40-4.60, p=0.002) while MLD, MDS-related cytogenetics and previous MDS history did not influence OS. We conclude that ASXL1 and TP53 mutations identify two molecular subgroups among AML-MRCs, with specific poor prognosis. This could be useful for future diagnostic and prognostic classifications. Impact Journals LLC 2015-02-28 /pmc/articles/PMC4480760/ /pubmed/25860933 Text en Copyright: © 2015 Devillier et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Clinical Research Paper Devillier, Raynier Mansat-De Mas, Véronique Gelsi-Boyer, Veronique Demur, Cecile Murati, Anne Corre, Jill Prebet, Thomas Bertoli, Sarah Brecqueville, Mandy Arnoulet, Christine Recher, Christian Vey, Norbert Mozziconacci, Marie-Joelle Delabesse, Eric Birnbaum, Daniel Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes |
title | Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes |
title_full | Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes |
title_fullStr | Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes |
title_full_unstemmed | Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes |
title_short | Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes |
title_sort | role of asxl1 and tp53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes |
topic | Clinical Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480760/ https://www.ncbi.nlm.nih.gov/pubmed/25860933 |
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