Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia

Abstract 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 compan...

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Autores principales:	Shujuan Wang, Zhenzhen Wu, Tao Li, Yafei Li, Weiqiong Wang, Qianqian Hao, Xinsheng Xie, Dingming Wan, Zhongxing Jiang, Chong Wang, Yanfang Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/270fb347cb7e47d096b6fa223960d43d
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spelling	oai:doaj.org-article:270fb347cb7e47d096b6fa223960d43d2021-12-02T17:55:13ZMutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia10.1038/s41598-020-69194-62045-2322https://doaj.org/article/270fb347cb7e47d096b6fa223960d43d2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-69194-6https://doaj.org/toc/2045-2322Abstract 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.Shujuan WangZhenzhen WuTao LiYafei LiWeiqiong WangQianqian HaoXinsheng XieDingming WanZhongxing JiangChong WangYanfang LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shujuan Wang Zhenzhen Wu Tao Li Yafei Li Weiqiong Wang Qianqian Hao Xinsheng Xie Dingming Wan Zhongxing Jiang Chong Wang Yanfang Liu Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia
description	Abstract 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.
format	article
author	Shujuan Wang Zhenzhen Wu Tao Li Yafei Li Weiqiong Wang Qianqian Hao Xinsheng Xie Dingming Wan Zhongxing Jiang Chong Wang Yanfang Liu
author_facet	Shujuan Wang Zhenzhen Wu Tao Li Yafei Li Weiqiong Wang Qianqian Hao Xinsheng Xie Dingming Wan Zhongxing Jiang Chong Wang Yanfang Liu
author_sort	Shujuan Wang
title	Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia
title_short	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_sort	mutational spectrum and prognosis in nras-mutated acute myeloid leukemia
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/270fb347cb7e47d096b6fa223960d43d
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Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia

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