新一代测序揭示了新诊断急性髓性白血病患者接受 CAG 方案联合地西他滨治疗后的复发和无白血病生存风险

Sai Huang , Peng Chen , Lu Wang , Lingmin Xu , Nan Wang , Fei Li , Liping Dou , Daihong Liu
{"title":"新一代测序揭示了新诊断急性髓性白血病患者接受 CAG 方案联合地西他滨治疗后的复发和无白血病生存风险","authors":"Sai Huang ,&nbsp;Peng Chen ,&nbsp;Lu Wang ,&nbsp;Lingmin Xu ,&nbsp;Nan Wang ,&nbsp;Fei Li ,&nbsp;Liping Dou ,&nbsp;Daihong Liu","doi":"10.1016/j.cpt.2023.10.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers. Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities, as well as those with specific gene mutations. However, the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well defined. Therefore, this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with AML.</p></div><div><h3>Methods</h3><p>This study analyzed the clinical data and genetic mutations based on next-generation sequencing (NGS) in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army (PLA) General Hospital from January 2008 to August 2020. Factors associated with the cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) in patients newly diagnosed with AML were analyzed.</p></div><div><h3>Results</h3><p>The most adverse prognosis of DCAG-treated patients was observed in those with <em>FLT3-ITD, KIT, PTPN11, GATA2,</em> or <em>IDH1</em> mutations during univariable analysis, whereas <em>PTPN11</em> mutation was solely significant in multivariable analysis, with an increased likelihood of CIR (<em>P</em> = 0.001) and reduced LFS duration (<em>P</em> = 0.077). Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk (<em>P</em> = 0.044) and decreased LFS duration (<em>P</em> = 0.042) in multivariable analysis. In this study, we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age range.</p></div><div><h3>Conclusion</h3><p>NGS demonstrated a dismal overall outcome in patients with the rare <em>PTPN11</em> mutations, indicating the need for new therapies that target this high-risk subtype of AML. These results offer a potential molecular stratification and treatment guidance for patients with AML.</p></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000848/pdfft?md5=13d16b5f18f63a5affe5cfcce3185123&pid=1-s2.0-S2949713223000848-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Next-generation sequencing reveals relapse and leukemia-free survival risks in newly diagnosed acute myeloid leukemia treated with CAG regimen combined with decitabine\",\"authors\":\"Sai Huang ,&nbsp;Peng Chen ,&nbsp;Lu Wang ,&nbsp;Lingmin Xu ,&nbsp;Nan Wang ,&nbsp;Fei Li ,&nbsp;Liping Dou ,&nbsp;Daihong Liu\",\"doi\":\"10.1016/j.cpt.2023.10.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers. Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities, as well as those with specific gene mutations. However, the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well defined. Therefore, this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with AML.</p></div><div><h3>Methods</h3><p>This study analyzed the clinical data and genetic mutations based on next-generation sequencing (NGS) in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army (PLA) General Hospital from January 2008 to August 2020. Factors associated with the cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) in patients newly diagnosed with AML were analyzed.</p></div><div><h3>Results</h3><p>The most adverse prognosis of DCAG-treated patients was observed in those with <em>FLT3-ITD, KIT, PTPN11, GATA2,</em> or <em>IDH1</em> mutations during univariable analysis, whereas <em>PTPN11</em> mutation was solely significant in multivariable analysis, with an increased likelihood of CIR (<em>P</em> = 0.001) and reduced LFS duration (<em>P</em> = 0.077). Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk (<em>P</em> = 0.044) and decreased LFS duration (<em>P</em> = 0.042) in multivariable analysis. In this study, we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age range.</p></div><div><h3>Conclusion</h3><p>NGS demonstrated a dismal overall outcome in patients with the rare <em>PTPN11</em> mutations, indicating the need for new therapies that target this high-risk subtype of AML. These results offer a potential molecular stratification and treatment guidance for patients with AML.</p></div>\",\"PeriodicalId\":93920,\"journal\":{\"name\":\"Cancer pathogenesis and therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-10-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2949713223000848/pdfft?md5=13d16b5f18f63a5affe5cfcce3185123&pid=1-s2.0-S2949713223000848-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer pathogenesis and therapy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2949713223000848\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer pathogenesis and therapy","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2949713223000848","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

背景急性髓性白血病(AML)是一种异质性造血恶性肿瘤,其预后与多种生物标志物有关。地西他滨是一种脱氧核糖核酸(DNA)甲基转移酶(DNMT)抑制剂,与阿糖胞苷、盐酸阿克拉比星和粒细胞集落刺激因子(DCAG)联合使用,已被用于新诊断的急性髓细胞白血病患者。这种疗法尤其适用于年龄较大、免疫力低下或合并疾病的脆弱患者,以及有特定基因突变的患者。然而,分子风险分层与 DCAG 方案治疗指导的整合尚未得到很好的界定。因此,本研究旨在调查与急性髓细胞性白血病相关的基因突变,并为新诊断的急性髓细胞性白血病患者制定合适的治疗策略。方法本研究分析了2008年1月至2020年8月期间在中国人民解放军总医院接受DCAG方案治疗的124例新诊断急性髓细胞性白血病患者的临床数据和基于新一代测序(NGS)的基因突变。分析了与新诊断的急性髓细胞白血病患者的累积复发率(CIR)和无白血病生存期(LFS)相关的因素。结果 在单变量分析中,FLT3-ITD、KIT、PTPN11、GATA2或IDH1突变的患者预后最差,而在多变量分析中,PTPN11突变唯一显著,CIR可能性增加(P = 0.001),无白血病生存期缩短(P = 0.077)。在多变量分析中,高白细胞仍是 CIR 风险增加(P = 0.044)和 LFS 持续时间缩短(P = 0.042)的独立风险因素。在这项研究中,我们验证了接受基于表观遗传修饰剂的诱导方案的急性髓细胞性白血病患者在广泛的年龄范围内的风险分级。结论NGS显示了罕见的PTPN11突变患者的总体预后不佳,这表明需要针对这一高风险急性髓细胞性白血病亚型的新疗法。这些结果为急性髓细胞性白血病患者提供了潜在的分子分层和治疗指导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Next-generation sequencing reveals relapse and leukemia-free survival risks in newly diagnosed acute myeloid leukemia treated with CAG regimen combined with decitabine

Background

Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers. Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities, as well as those with specific gene mutations. However, the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well defined. Therefore, this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with AML.

Methods

This study analyzed the clinical data and genetic mutations based on next-generation sequencing (NGS) in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army (PLA) General Hospital from January 2008 to August 2020. Factors associated with the cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) in patients newly diagnosed with AML were analyzed.

Results

The most adverse prognosis of DCAG-treated patients was observed in those with FLT3-ITD, KIT, PTPN11, GATA2, or IDH1 mutations during univariable analysis, whereas PTPN11 mutation was solely significant in multivariable analysis, with an increased likelihood of CIR (P = 0.001) and reduced LFS duration (P = 0.077). Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk (P = 0.044) and decreased LFS duration (P = 0.042) in multivariable analysis. In this study, we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age range.

Conclusion

NGS demonstrated a dismal overall outcome in patients with the rare PTPN11 mutations, indicating the need for new therapies that target this high-risk subtype of AML. These results offer a potential molecular stratification and treatment guidance for patients with AML.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cancer pathogenesis and therapy
Cancer pathogenesis and therapy Surgery, Radiology and Imaging, Cancer Research, Oncology
CiteScore
0.80
自引率
0.00%
发文量
0
审稿时长
54 days
期刊最新文献
Table of Contents Cover Corrigendum to “Gene mutations in newly diagnosed multiple myeloma patients detected by next-generation sequencing technology” [Cancer Pathog Ther. 2024;2:205–211] Table of Contents Current and future perspectives on the regulation and functions of miR-545 in cancer development
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1