Gene mutation profile in patients with acquired pure red cell aplasia
Gene mutation profile in patients with acquired pure red cell aplasia
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获得性纯红细胞再生障碍性贫血患者的基因突变谱
DOI：
10.1007/s00277-020-04154-8
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发表时间：
2020-06-27
影响因子：
3.5
通讯作者：
Han, Bing
中科院分区：
文献类型：
--
作者：
Long, Zhangbiao;Li, Hongmin;Han, Bing
获得性纯红细胞再生障碍性贫血（PRCA）是一种以正常红细胞贫血伴网织红细胞减少和缺乏成红细胞为特征的疾病。获得性PRCA的基因突变谱尚未确定。在这项研究中，我们的目的是确定获得性PRCA患者的基因突变谱和基因突变与免疫抑制治疗（IST）反应之间的相关性。30例新诊断的获得性PRCA患者入组本研究，然后对这些患者和一组93个与其他骨髓衰竭相关的候选基因进行全外显子组测序，以进行以下分析。随后患者接受IST治疗至少2年。IST组中位治疗8个月（6-10个月）时，完全缓解13例，部分缓解10例（ORR76.7%），无效7例。在16例患者中检测到15个基因的23个突变（53%）。突变基因与转录、信号转导和表观遗传调控途径有关。点突变中最常见的转换是C > T。年龄、性别、确诊时血红蛋白水平、基因突变与否对IST疗效无影响。然而，尽管BCOR或BCORL 1突变患者对IST的反应与无突变患者相似（P= 0.235），但其反应优于其他基因突变患者（P= 0.0193）。总之，获得性PRCA患者可能存在克隆性基因突变。BCOR和BCORL 1基因突变患者对IST的反应可能优于其他基因突变患者。
Acquired pure red cell aplasia (PRCA) is a disorder characterized by normocytic anemia associated with reticulocytopenia and an absence of erythroblasts. The gene mutation profile in acquired PRCA is not defined yet. In this study, we aimed to identify the gene mutation spectrum of patients with acquired PRCA and the correlation between gene mutations and response to immunosuppressive therapy (IST). Thirty newly diagnosed acquired PRCA patients were enrolled in this study, and then whole-exome sequencing were performed among these patients and a panel with 93 candidate genes which associated with other bone marrow failure for the following analysis. Subsequently patients were treated with IST for at least 2 years. When treated with IST, there were thirteen complete response, ten partial response (ORR 76.7%), and seven no response at a medium of 8 (6–10) months. Totally twenty-three mutations in fifteen genes were detected in sixteen patients (53%). The mutated genes were associated with transcription, signal transduction, and epigenetic regulation pathways. The most frequent transitions in the point mutations were C > T. Age, gender, hemoglobin level at diagnosis, and gene mutation or not did not influence the response to IST. However, although patients withBCOR or BCORL1mutations had a similar response to IST compared with those without mutation (P= 0.235), they had a better response than those with other gene mutations (P= 0.0193). In conclusion, patients with acquired PRCA may have clonal gene mutations. The patients withBCORandBCORL1mutations may suggest a better response to IST compared with those with other mutations.