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Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia

The mutational spectrum and prognostic factors of NRAS-mutated (NRAS(mut)) acute myeloid leukemia (AML) are largely unknown. We performed next-generation sequencing (NGS) in 1,149 cases of de novo AML and discovered 152 NRAS(mut) AML (13%). Of the 152 NRAS(mut) AML, 89% had at least one companion mu...

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Autores principales: Wang, Shujuan, Wu, Zhenzhen, Li, Tao, Li, Yafei, Wang, Weiqiong, Hao, Qianqian, Xie, Xinsheng, Wan, Dingming, Jiang, Zhongxing, Wang, Chong, Liu, Yanfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376066/
https://www.ncbi.nlm.nih.gov/pubmed/32699322
http://dx.doi.org/10.1038/s41598-020-69194-6
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author Wang, Shujuan
Wu, Zhenzhen
Li, Tao
Li, Yafei
Wang, Weiqiong
Hao, Qianqian
Xie, Xinsheng
Wan, Dingming
Jiang, Zhongxing
Wang, Chong
Liu, Yanfang
author_facet Wang, Shujuan
Wu, Zhenzhen
Li, Tao
Li, Yafei
Wang, Weiqiong
Hao, Qianqian
Xie, Xinsheng
Wan, Dingming
Jiang, Zhongxing
Wang, Chong
Liu, Yanfang
author_sort Wang, Shujuan
collection PubMed
description The mutational spectrum and prognostic factors of NRAS-mutated (NRAS(mut)) acute myeloid leukemia (AML) are largely unknown. We performed next-generation sequencing (NGS) in 1,149 cases of de novo AML and discovered 152 NRAS(mut) AML (13%). Of the 152 NRAS(mut) AML, 89% had at least one companion mutated gene. DNA methylation-related genes confer up to 62% incidence. TET2 had the highest mutation frequency (51%), followed by ASXL1 (17%), NPM1 (14%), CEBPA (13%), DNMT3A (13%), FLT3-ITD (11%), KIT (11%), IDH2 (9%), RUNX1 (8%), U2AF1 (7%) and SF3B1(5%). Multivariate analysis suggested that age ≥ 60 years and mutations in U2AF1 were independent factors related to failure to achieve complete remission after induction therapy. Age ≥ 60 years, non-M3 types and U2AF1 mutations were independent prognostic factors for poor overall survival. Age ≥ 60 years, non-M3 types and higher risk group were independent prognostic factors for poor event-free survival (EFS) while allogenic hematopoietic stem cell transplantation was an independent prognostic factor for good EFS. Our study provided new insights into the mutational spectrum and prognostic factors of NRAS(mut) AML.
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spelling pubmed-73760662020-07-24 Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia Wang, Shujuan Wu, Zhenzhen Li, Tao Li, Yafei Wang, Weiqiong Hao, Qianqian Xie, Xinsheng Wan, Dingming Jiang, Zhongxing Wang, Chong Liu, Yanfang Sci Rep Article The mutational spectrum and prognostic factors of NRAS-mutated (NRAS(mut)) acute myeloid leukemia (AML) are largely unknown. We performed next-generation sequencing (NGS) in 1,149 cases of de novo AML and discovered 152 NRAS(mut) AML (13%). Of the 152 NRAS(mut) AML, 89% had at least one companion mutated gene. DNA methylation-related genes confer up to 62% incidence. TET2 had the highest mutation frequency (51%), followed by ASXL1 (17%), NPM1 (14%), CEBPA (13%), DNMT3A (13%), FLT3-ITD (11%), KIT (11%), IDH2 (9%), RUNX1 (8%), U2AF1 (7%) and SF3B1(5%). Multivariate analysis suggested that age ≥ 60 years and mutations in U2AF1 were independent factors related to failure to achieve complete remission after induction therapy. Age ≥ 60 years, non-M3 types and U2AF1 mutations were independent prognostic factors for poor overall survival. Age ≥ 60 years, non-M3 types and higher risk group were independent prognostic factors for poor event-free survival (EFS) while allogenic hematopoietic stem cell transplantation was an independent prognostic factor for good EFS. Our study provided new insights into the mutational spectrum and prognostic factors of NRAS(mut) AML. Nature Publishing Group UK 2020-07-22 /pmc/articles/PMC7376066/ /pubmed/32699322 http://dx.doi.org/10.1038/s41598-020-69194-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Shujuan
Wu, Zhenzhen
Li, Tao
Li, Yafei
Wang, Weiqiong
Hao, Qianqian
Xie, Xinsheng
Wan, Dingming
Jiang, Zhongxing
Wang, Chong
Liu, Yanfang
Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia
title Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia
title_full Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia
title_fullStr Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia
title_full_unstemmed Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia
title_short Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia
title_sort mutational spectrum and prognosis in nras-mutated acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376066/
https://www.ncbi.nlm.nih.gov/pubmed/32699322
http://dx.doi.org/10.1038/s41598-020-69194-6
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