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The impact of DNMT3A variant allele frequency and two different comutations on patients with de novo cytogenetically normal acute myeloid leukemia
To refine the biological and prognostic significance of DNMT3A mutations in acute myeloid leukemia (AML), we assessed the impact of DNMT3A variant allele frequency (VAF) and its comutations in this study. Using targeted next‐generation sequencing, we analyzed 171 adult patients with de novo cytogene...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225240/ https://www.ncbi.nlm.nih.gov/pubmed/36912186 http://dx.doi.org/10.1002/cam4.5764 |
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author | Chen, Xian Tian, Chuchu Hao, Zhuanghui Pan, Lingang Hong, Minglin Wei, Wei Muyey, Daniel Muteb Wang, Hongwei Chen, Xiuhua |
author_facet | Chen, Xian Tian, Chuchu Hao, Zhuanghui Pan, Lingang Hong, Minglin Wei, Wei Muyey, Daniel Muteb Wang, Hongwei Chen, Xiuhua |
author_sort | Chen, Xian |
collection | PubMed |
description | To refine the biological and prognostic significance of DNMT3A mutations in acute myeloid leukemia (AML), we assessed the impact of DNMT3A variant allele frequency (VAF) and its comutations in this study. Using targeted next‐generation sequencing, we analyzed 171 adult patients with de novo cytogenetically normal AML for DNMT3A mutations and associated comutations. DNMT3A (mut) was detected in 35 patients. DNMT3A (mut) patients were divided into DNMT3A (High) and DNMT3A (Low) using a cut‐off VAF value of 42%. We observed that DNMT3A (High) patients at diagnosis had increasing white blood cell (WBC) counts (p < 0.001) and a higher lactate dehydrogenase (LDH) level (p = 0.027), and were associated with lower complete remission (CR) rate (p = 0.015) and shorter overall survival (OS) (p = 0.032) than DNMT3A (Low) patients. We classified two different comutated genetypes, including DNMT3A (mut) NPM1 (mut) FLT3‐ITD (mut) and DNMT3A (mut) IDH1/IDH2 (mut). Patients with DNMT3A (mut) NPM1 (mut) FLT3‐ITD (mut) showed worse OS (p = 0.026) and relapse‐free survival (RFS) (p = 0.003) than those with DNMT3A (mut) IDH1/IDH2 (mut), and showed a shorter OS (p = 0.027) than those with DNMT3A (wt) NPM1 (mut) FLT3‐ITD (mut). We also observed that patients with DNMT3A (mut) IDH1/IDH2 (mut) had higher platelet counts (p = 0.009) and a lower BM blast percentage (p = 0.040) than those with DNMT3A (wt) IDH1/IDH2 (mut). In multivariate analyses, DNMT3A (High) was independently associated with a lower CR rate (OR = 5.883; p = 0.004) and shorter OS (HR = 3.768; p < 0.001). DNMT3A (mut) NPM1 (mut) FLT3‐ITD (mut) independently affected worse OS (HR = 6.030; p < 0.001) and RFS (HR = 8.939; p < 0.001). Our findings might be potentially useful for predicting clinical outcomes. |
format | Online Article Text |
id | pubmed-10225240 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102252402023-05-29 The impact of DNMT3A variant allele frequency and two different comutations on patients with de novo cytogenetically normal acute myeloid leukemia Chen, Xian Tian, Chuchu Hao, Zhuanghui Pan, Lingang Hong, Minglin Wei, Wei Muyey, Daniel Muteb Wang, Hongwei Chen, Xiuhua Cancer Med RESEARCH ARTICLES To refine the biological and prognostic significance of DNMT3A mutations in acute myeloid leukemia (AML), we assessed the impact of DNMT3A variant allele frequency (VAF) and its comutations in this study. Using targeted next‐generation sequencing, we analyzed 171 adult patients with de novo cytogenetically normal AML for DNMT3A mutations and associated comutations. DNMT3A (mut) was detected in 35 patients. DNMT3A (mut) patients were divided into DNMT3A (High) and DNMT3A (Low) using a cut‐off VAF value of 42%. We observed that DNMT3A (High) patients at diagnosis had increasing white blood cell (WBC) counts (p < 0.001) and a higher lactate dehydrogenase (LDH) level (p = 0.027), and were associated with lower complete remission (CR) rate (p = 0.015) and shorter overall survival (OS) (p = 0.032) than DNMT3A (Low) patients. We classified two different comutated genetypes, including DNMT3A (mut) NPM1 (mut) FLT3‐ITD (mut) and DNMT3A (mut) IDH1/IDH2 (mut). Patients with DNMT3A (mut) NPM1 (mut) FLT3‐ITD (mut) showed worse OS (p = 0.026) and relapse‐free survival (RFS) (p = 0.003) than those with DNMT3A (mut) IDH1/IDH2 (mut), and showed a shorter OS (p = 0.027) than those with DNMT3A (wt) NPM1 (mut) FLT3‐ITD (mut). We also observed that patients with DNMT3A (mut) IDH1/IDH2 (mut) had higher platelet counts (p = 0.009) and a lower BM blast percentage (p = 0.040) than those with DNMT3A (wt) IDH1/IDH2 (mut). In multivariate analyses, DNMT3A (High) was independently associated with a lower CR rate (OR = 5.883; p = 0.004) and shorter OS (HR = 3.768; p < 0.001). DNMT3A (mut) NPM1 (mut) FLT3‐ITD (mut) independently affected worse OS (HR = 6.030; p < 0.001) and RFS (HR = 8.939; p < 0.001). Our findings might be potentially useful for predicting clinical outcomes. John Wiley and Sons Inc. 2023-03-13 /pmc/articles/PMC10225240/ /pubmed/36912186 http://dx.doi.org/10.1002/cam4.5764 Text en © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | RESEARCH ARTICLES Chen, Xian Tian, Chuchu Hao, Zhuanghui Pan, Lingang Hong, Minglin Wei, Wei Muyey, Daniel Muteb Wang, Hongwei Chen, Xiuhua The impact of DNMT3A variant allele frequency and two different comutations on patients with de novo cytogenetically normal acute myeloid leukemia |
title | The impact of
DNMT3A
variant allele frequency and two different comutations on patients with de novo cytogenetically normal acute myeloid leukemia |
title_full | The impact of
DNMT3A
variant allele frequency and two different comutations on patients with de novo cytogenetically normal acute myeloid leukemia |
title_fullStr | The impact of
DNMT3A
variant allele frequency and two different comutations on patients with de novo cytogenetically normal acute myeloid leukemia |
title_full_unstemmed | The impact of
DNMT3A
variant allele frequency and two different comutations on patients with de novo cytogenetically normal acute myeloid leukemia |
title_short | The impact of
DNMT3A
variant allele frequency and two different comutations on patients with de novo cytogenetically normal acute myeloid leukemia |
title_sort | impact of
dnmt3a
variant allele frequency and two different comutations on patients with de novo cytogenetically normal acute myeloid leukemia |
topic | RESEARCH ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225240/ https://www.ncbi.nlm.nih.gov/pubmed/36912186 http://dx.doi.org/10.1002/cam4.5764 |
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