Blood:老年贫血个体的突变谱和克隆造血动态

2020-02-14 QQY MedSci原创

中心点:特异性突变,包括TP53和SF3B1,在老年贫血个体中富集,但不包括DNMT3A、TET2和ASXL1。一般来说,随着时间的推移,克隆只会带来有限的选择优势,这与特定的驱动基因有差异。摘要:贫血是一种造血老化的主要的、目前知之甚少的临床表现。随着年龄增长,携带获得性白血病相关突变的造血克隆扩增到可被检测到,被称为克隆造血(CH)。为了研究老年贫血与CH的关系,Zeventer等人对老年贫血

中心点:

特异性突变,包括TP53和SF3B1,在老年贫血个体中富集,但不包括DNMT3A、TET2和ASXL1。

一般来说,随着时间的推移,克隆只会带来有限的选择优势,这与特定的驱动基因有差异。

摘要:

贫血是一种造血老化的主要的、目前知之甚少的临床表现。随着年龄增长,携带获得性白血病相关突变的造血克隆扩增到可被检测到,被称为克隆造血(CH)。为了研究老年贫血与CH的关系,Zeventer等人对老年贫血个体CH的分布和动态进行了研究。

从前瞻性的以人群为基础的队列研究中,研究人员根据WHO标准和1:1匹配对照筛选了676位60岁及以上的贫血个体。对1298例外周血中27个驱动基因的突变等位基因频率(VAF)≥1%的获得性变异进行分析。为了追踪克隆进化随时间的变化,研究人员纳入了所有可用的随访样本(943例)。

与对照组相比,CH在贫血个体中更常见(46.6% vs 39.1%,P=0.007)。虽然在贫血个体中常见的DTA突变(DNMT3A、TET2、ASXL1)与对照组相比没有差异,但贫血队列中富集的其他突变,包括TP53和SF3B1。与营养不良患者不同,慢性炎性贫血和原因不明的贫血患者的CH患病率高于对照组。随访分析显示,在44个月内,无论有无贫血,克隆的扩增和衰退一般只会有轻微的VAF增长(平均0.56%)。特异性突变与不同的生长速度和获得额外打击的倾向性相关。

与不影响总体生存的小概率克隆(<5% VAF)相比,较大概率克隆与死亡风险增加相关。

原始出处:

Isabelle A. van Zeventer, et al.Mutational spectrum and dynamics of clonal hematopoiesis in anemia of older individuals.Blood. February 13, 2020.

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    2020-07-03 aids221
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    2020-02-16 俅侠
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