亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Predicting cytopenias, progression, and survival in patients with clonal cytopenia of undetermined significance: a prospective cohort study

医学 细胞减少 内科学 恶性肿瘤 前瞻性队列研究 队列 回顾性队列研究 血液恶性肿瘤 队列研究 肿瘤科 儿科 骨髓
作者
Catherine Cargo,Elsa Bernard,Tumas Beinortas,Kelly L. Bolton,Paul Glover,Helen Warren,Daniel Payne,Rukhsaar Ali,Alesia Khan,Mike Short,Suzan Van Hoppe,Alexandra Smith,Jan Taylor,Paul Evans,Elli Papaemmanuil,Simon Crouch
出处
期刊:The Lancet Haematology [Elsevier BV]
卷期号:11 (1): e51-e61 被引量:12
标识
DOI:10.1016/s2352-3026(23)00340-x
摘要

Background Somatic mutations are frequently reported in individuals with cytopenia but without a confirmed haematological diagnosis (clonal cytopenia of undetermined significance; CCUS). These patients have an increased risk of progression to a myeloid malignancy and worse overall survival than those with no such mutations. To date, studies have been limited by retrospective analysis or small patient numbers. We aimed to establish the natural history of CCUS by prospectively investigating outcome in a large, well defined patient cohort. Methods This prospective cohort study was conducted at the Haematological Malignancy Diagnostic Service, a diagnostic laboratory in Leeds, UK. Patients aged at least 18 years who were referred for investigation of cytopenia were eligible for inclusion; those with a history of myeloid malignancy were not eligible. Targeted sequencing was conducted alongside routine clinical testing. Baseline mutation analysis was then correlated with the main study outcomes: longitudinal blood counts, disease progression to a myeloid malignancy, and overall survival with a median follow-up of 4·54 years (IQR 4·03–5·04). Data were collected manually from hospital records or extracted from laboratory or clinical outcome databases. Findings Bone marrow samples from 2348 patients were received at the Haematological Malignancy Diagnostic Service between July 1, 2014, and July 31, 2016. Of these, 2083 patients (median age 72 years [IQR 63–80, range 18–99]; 854 [41·0%] female and 1229 [59·0%] male) met the inclusion criteria and had samples of sufficient quality for further analysis. 598 (28·7%) patients received a diagnosis on the basis of their biopsy sample, whereas 1485 (71·3%) samples were classified as non-diagnostic; of these, CCUS was confirmed in 400 (26·9%) patients (256 [64·0%] male and 144 [36·0%] female). TET2, SRSF2, and DNMT3A were the most frequently mutated genes in patients with CCUS, with 320 (80%) of 400 patients harbouring a mutation in at least one of these genes. Age (p<0·0001), sex (p=0·0027), and mutations in ASXL1 (p=0·0009), BCOR (p=0·0056), and TP53 (p=0·0055) correlated with a worse overall survival; however, the number of mutations was the strongest predictor for progression to a myeloid malignancy (two mutations, p=0·0024; three or more mutations, p=0·0004). Extended sequencing of samples from a subgroup of patients with sequential samples and no mutations in the initial myeloid gene panel showed recurrent mutations in both DDX41 and UBA1, suggesting that these genes should be included in clinical test panels. Interpretation Mutation analysis is advised in patients who have undergone bone marrow examination and have an otherwise-unexplained cytopenia. High-risk genetic mutations and increased numbers of mutations are predictive of both survival and progression within 5 years of presentation, warranting clinical surveillance and, when necessary, intervention. Funding MDS Foundation.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
可爱的函函应助鲅鱼圈采纳,获得10
12秒前
14秒前
lzzz发布了新的文献求助10
21秒前
英喆完成签到 ,获得积分10
21秒前
我是老大应助畅快的毛衣采纳,获得10
36秒前
45秒前
47秒前
鲅鱼圈发布了新的文献求助10
50秒前
50秒前
Leofar完成签到 ,获得积分10
57秒前
58秒前
鲅鱼圈完成签到,获得积分10
1分钟前
h0jian09完成签到,获得积分10
1分钟前
BaooooooMao完成签到,获得积分10
1分钟前
愉快的犀牛完成签到 ,获得积分10
1分钟前
Sunny完成签到,获得积分10
2分钟前
yujie完成签到 ,获得积分10
2分钟前
赘婿应助科研通管家采纳,获得10
2分钟前
2分钟前
西柚柠檬完成签到 ,获得积分10
3分钟前
心系天下完成签到 ,获得积分10
3分钟前
Alex-Song完成签到 ,获得积分0
3分钟前
不秃燃的小老弟完成签到 ,获得积分10
4分钟前
4分钟前
Owen应助科研通管家采纳,获得10
4分钟前
年年有余完成签到,获得积分10
5分钟前
胖小羊完成签到 ,获得积分10
5分钟前
6分钟前
领导范儿应助科研通管家采纳,获得10
6分钟前
7分钟前
juan完成签到 ,获得积分10
8分钟前
学术小垃圾完成签到,获得积分10
8分钟前
叁月二完成签到 ,获得积分10
8分钟前
8分钟前
科研通AI2S应助科研通管家采纳,获得10
8分钟前
大模型应助科研通管家采纳,获得10
8分钟前
xingsixs完成签到 ,获得积分10
9分钟前
AprilLeung完成签到 ,获得积分10
10分钟前
10分钟前
深情安青应助科研通管家采纳,获得10
10分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3990423
求助须知:如何正确求助?哪些是违规求助? 3532158
关于积分的说明 11256513
捐赠科研通 3271046
什么是DOI,文献DOI怎么找? 1805207
邀请新用户注册赠送积分活动 882302
科研通“疑难数据库(出版商)”最低求助积分说明 809234