Prognostic Significance of Comprehensive Gene Mutations and Clinical Characteristics in Adult T-Cell Acute Lymphoblastic Leukemia Based on Next-Generation Sequencing.
Prognostic Significance of Comprehensive Gene Mutations and Clinical Characteristics in Adult T-Cell Acute Lymphoblastic Leukemia Based on Next-Generation Sequencing.
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DOI：
10.3389/fonc.2022.811151
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发表时间：
2022
影响因子：
4.7
通讯作者：
Wu Q
中科院分区：
文献类型：
--
作者：
Yin H;Hong M;Deng J;Yao L;Qian C;Teng Y;Li T;Wu Q
成人T细胞急性淋巴细胞白血病(T-ALL)是一种预后不良的异质性恶性肿瘤。然而，准确的预后分层因素仍不清楚。收集90例成人T细胞急性淋巴细胞白血病/淋巴瘤(T-ALL/LBL)患者的临床资料。回顾分析下一代测序检测到的基因突变和临床特征与T-ALL/LBL患者预后的关系，通过COX比例风险模型建立三种新的风险分层模型。共鉴定出47个突变基因。73.3%的患者至少有一个突变，36.7%的患者有≥3突变。突变频率较高的基因有NOTCH1、FBXW7和DNMT3A。改变最多的信号通路是Notch通路、转录调控通路和DNA甲基化通路。将年龄(45岁)、血小板(50G/L)、乳酸脱氢酶(600U/L)、D19-BMR检测反应、TP53和细胞周期信号通路改变、造血干细胞移植纳入无事件生存的危险分层模型。将年龄(45岁)、白细胞计数(30G/L)、D19-BMR检测反应、TP53和细胞周期信号通路改变、造血干细胞移植纳入总体生存(OS)的危险分层模型。根据我们的风险分层模型，低风险组的1年EFS和OS率显著高于高风险组。我们的风险分层模型在成人T-ALL/LBL患者中显示出良好的预后作用，并可能指导个体化治疗并最终改善他们的预后。
Adult T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignant tumor with poor prognosis. However, accurate prognostic stratification factors are still unclear. Data from 90 adult T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients were collected. The association of gene mutations detected by next-generation sequencing and clinical characteristics with the outcomes of T-ALL/LBL patients were retrospectively analyzed to build three novel risk stratification models through Cox proportional hazards model. Forty-seven mutated genes were identified. Here, 73.3% of patients had at least one mutation, and 36.7% had ≥3 mutations. The genes with higher mutation frequency were NOTCH1, FBXW7, and DNMT3A. The most frequently altered signaling pathways were NOTCH pathway, transcriptional regulation pathway, and DNA methylation pathway. Age (45 years old), platelet (PLT) (50 G/L), actate dehydrogenase (LDH) (600 U/L), response in D19-BMR detection, TP53 and cell cycle signaling pathway alterations, and hematopoietic stem cell transplantation (HSCT) were integrated into a risk stratification model of event-free survival (EFS). Age (45 years old), white blood cell (WBC) count (30 G/L), response in D19-BMR detection, TP53 and cell cycle signaling pathway alterations, and HSCT were integrated into a risk stratification model of overall survival (OS). According to our risk stratification models, the 1-year EFS and OS rates in the low-risk group were significantly higher than those in the high-risk group. Our risk stratification models exhibited good prognostic roles in adult T-ALL/LBL patients and might guide individualized treatment and ultimately improve their outcomes.
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影响因子：
64.8
作者：
Chen, Zhao;Cheng, Katherine;Walton, Zandra;Wang, Yuchuan;Ebi, Hiromichi;Shimamura, Takeshi;Liu, Yan;Tupper, Tanya;Ouyang, Jing;Li, Jie;Gao, Peng;Woo, Michele S.;Xu, Chunxiao;Yanagita, Masahiko;Altabef, Abigail;Wang, Shumei;Lee, Charles;Nakada, Yuji;Pena, Christopher G.;Sun, Yanping;Franchetti, Yoko;Yao, Catherine;Saur, Amy;Cameron, Michael D.;Nishino, Mizuki;Hayes, D. Neil;Wilkerson, Matthew D.;Roberts, Patrick J.;Lee, Carrie B.;Bardeesy, Nabeel;Butaney, Mohit;Chirieac, Lucian R.;Costa, Daniel B.;Jackman, David;Sharpless, Norman E.;Castrillon, Diego H.;Demetri, George D.;Jaenne, Pasi A.;Pandolfi, Pier Paolo;Cantley, Lewis C.;Kung, Andrew L.;Engelman, Jeffrey A.;Wong, Kwok-Kin
通讯作者：
Wong, Kwok-Kin
影响因子：
28.4
作者：
Berry, Donald A.;Zhou, Shouhao;Radich, Jerald P.
通讯作者：
Radich, Jerald P.
影响因子：
3.1
作者：
Aref, Salah;El Agdar, Mohammed;Sabry, Mohamed
通讯作者：
Sabry, Mohamed
DOI：
10.1016/j.hemonc.2019.10.002
发表时间：
2021-09-01
期刊：
Hematology/oncology and stem cell therapy
影响因子：
--
作者：
Farhadfar, Nosha;Li, Ying;Adams, Carolyn Brooke
通讯作者：
Adams, Carolyn Brooke
DOI：
10.3324/haematol.2008.005272
发表时间：
2009-10-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Baldus, Claudia D.;Thibaut, Julia;Hofmann, Wolf-Karsten
通讯作者：
Hofmann, Wolf-Karsten