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Delineation of Molecular Lesions in Acute Myeloid Leukemia Patients at Diagnosis: Integrated Next Generation Sequencing and Cytogenomic Studies

Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by a wide range of genetic defects. Cytogenetics, molecular and genomic technologies have proved to be helpful for deciphering the mutational landscape of AML and impacted clinical practice. Forty-eight new AML patients were inve...

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Autores principales: Papuc, Sorina Mihaela, Erbescu, Alina, Cisleanu, Diana, Ozunu, Diana, Enache, Cristina, Dumitru, Ion, Lupoaia Andrus, Elena, Gaman, Mihaela, Popov, Viola Maria, Dobre, Maria, Stanca, Oana, Angelescu, Silvana, Berbec, Nicoleta, Colita, Andrei, Vladareanu, Ana-Maria, Bumbea, Horia, Arghir, Aurora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229708/
https://www.ncbi.nlm.nih.gov/pubmed/34070898
http://dx.doi.org/10.3390/genes12060846
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author Papuc, Sorina Mihaela
Erbescu, Alina
Cisleanu, Diana
Ozunu, Diana
Enache, Cristina
Dumitru, Ion
Lupoaia Andrus, Elena
Gaman, Mihaela
Popov, Viola Maria
Dobre, Maria
Stanca, Oana
Angelescu, Silvana
Berbec, Nicoleta
Colita, Andrei
Vladareanu, Ana-Maria
Bumbea, Horia
Arghir, Aurora
author_facet Papuc, Sorina Mihaela
Erbescu, Alina
Cisleanu, Diana
Ozunu, Diana
Enache, Cristina
Dumitru, Ion
Lupoaia Andrus, Elena
Gaman, Mihaela
Popov, Viola Maria
Dobre, Maria
Stanca, Oana
Angelescu, Silvana
Berbec, Nicoleta
Colita, Andrei
Vladareanu, Ana-Maria
Bumbea, Horia
Arghir, Aurora
author_sort Papuc, Sorina Mihaela
collection PubMed
description Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by a wide range of genetic defects. Cytogenetics, molecular and genomic technologies have proved to be helpful for deciphering the mutational landscape of AML and impacted clinical practice. Forty-eight new AML patients were investigated with an integrated approach, including classical and molecular cytogenetics, array-based comparative genomic hybridization and targeted next generation sequencing (NGS). Various genetic defects were identified in all the patients using our strategy. Targeted NGS revealed known pathogenic mutations as well as rare or unreported variants with deleterious predictions. The mutational screening of the normal karyotype (NK) group identified clinically relevant variants in 86.2% of the patients; in the abnormal cytogenetics group, the mutation detection rate was 87.5%. Overall, the highest mutation prevalence was observed for the NPM1 gene, followed by DNMT3A, FLT3 and NRAS. An unexpected co-occurrence of KMT2A translocation and DNMT3A-R882 was identified; alterations of these genes, which are involved in epigenetic regulation, are considered to be mutually exclusive. A microarray analysis detected CNVs in 25% of the NK AML patients. In patients with complex karyotypes, the microarray analysis made a significant contribution toward the accurate characterization of chromosomal defects. In summary, our results show that the integration of multiple investigative strategies increases the detection yield of genetic defects with potential clinical relevance.
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spelling pubmed-82297082021-06-26 Delineation of Molecular Lesions in Acute Myeloid Leukemia Patients at Diagnosis: Integrated Next Generation Sequencing and Cytogenomic Studies Papuc, Sorina Mihaela Erbescu, Alina Cisleanu, Diana Ozunu, Diana Enache, Cristina Dumitru, Ion Lupoaia Andrus, Elena Gaman, Mihaela Popov, Viola Maria Dobre, Maria Stanca, Oana Angelescu, Silvana Berbec, Nicoleta Colita, Andrei Vladareanu, Ana-Maria Bumbea, Horia Arghir, Aurora Genes (Basel) Article Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by a wide range of genetic defects. Cytogenetics, molecular and genomic technologies have proved to be helpful for deciphering the mutational landscape of AML and impacted clinical practice. Forty-eight new AML patients were investigated with an integrated approach, including classical and molecular cytogenetics, array-based comparative genomic hybridization and targeted next generation sequencing (NGS). Various genetic defects were identified in all the patients using our strategy. Targeted NGS revealed known pathogenic mutations as well as rare or unreported variants with deleterious predictions. The mutational screening of the normal karyotype (NK) group identified clinically relevant variants in 86.2% of the patients; in the abnormal cytogenetics group, the mutation detection rate was 87.5%. Overall, the highest mutation prevalence was observed for the NPM1 gene, followed by DNMT3A, FLT3 and NRAS. An unexpected co-occurrence of KMT2A translocation and DNMT3A-R882 was identified; alterations of these genes, which are involved in epigenetic regulation, are considered to be mutually exclusive. A microarray analysis detected CNVs in 25% of the NK AML patients. In patients with complex karyotypes, the microarray analysis made a significant contribution toward the accurate characterization of chromosomal defects. In summary, our results show that the integration of multiple investigative strategies increases the detection yield of genetic defects with potential clinical relevance. MDPI 2021-05-30 /pmc/articles/PMC8229708/ /pubmed/34070898 http://dx.doi.org/10.3390/genes12060846 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Papuc, Sorina Mihaela
Erbescu, Alina
Cisleanu, Diana
Ozunu, Diana
Enache, Cristina
Dumitru, Ion
Lupoaia Andrus, Elena
Gaman, Mihaela
Popov, Viola Maria
Dobre, Maria
Stanca, Oana
Angelescu, Silvana
Berbec, Nicoleta
Colita, Andrei
Vladareanu, Ana-Maria
Bumbea, Horia
Arghir, Aurora
Delineation of Molecular Lesions in Acute Myeloid Leukemia Patients at Diagnosis: Integrated Next Generation Sequencing and Cytogenomic Studies
title Delineation of Molecular Lesions in Acute Myeloid Leukemia Patients at Diagnosis: Integrated Next Generation Sequencing and Cytogenomic Studies
title_full Delineation of Molecular Lesions in Acute Myeloid Leukemia Patients at Diagnosis: Integrated Next Generation Sequencing and Cytogenomic Studies
title_fullStr Delineation of Molecular Lesions in Acute Myeloid Leukemia Patients at Diagnosis: Integrated Next Generation Sequencing and Cytogenomic Studies
title_full_unstemmed Delineation of Molecular Lesions in Acute Myeloid Leukemia Patients at Diagnosis: Integrated Next Generation Sequencing and Cytogenomic Studies
title_short Delineation of Molecular Lesions in Acute Myeloid Leukemia Patients at Diagnosis: Integrated Next Generation Sequencing and Cytogenomic Studies
title_sort delineation of molecular lesions in acute myeloid leukemia patients at diagnosis: integrated next generation sequencing and cytogenomic studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229708/
https://www.ncbi.nlm.nih.gov/pubmed/34070898
http://dx.doi.org/10.3390/genes12060846
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