小柯机器人

美国蒙特菲奥里医学中心Amit Verma、David J. Prezant、美国范德比尔特大学Michael R. Savona和美国罗格斯癌症研究所Advaitha Madireddy以及美国纽约大学格罗斯曼医学院医学系Anna Nolan研究组合作取得新进展。他们提出接触世界贸易中心 (WTC)灾难的首批急救人员中，克隆性造血 (CH)的负担很高。2022年3月7日，国际知名学术期刊《自然—医学》发表了这一成果。

他们表明，与接触WTC的消防员相比，血液样本的深度靶向测序表明显著更高比例的接触WTC的 CH 急救人员。在控制年龄、性别和种族/民族后。接触WTC的第一反应者的体细胞突变频率显示出与年龄相关的增加，主要影响 DNMT3A、TET2 和其他 CH 相关基因。类淋巴母细胞接触 WTC 颗粒物会导致体外常见脆弱部位的 DNA 复制失调。此外，用 WTC 颗粒物处理的小鼠在造血干细胞和祖细胞区室中产生了增加的突变负担。总之，接触WTC的第一反应者中 CH 的高负担为加强该人群的筛查和预防工作提供了理由。

据悉，对WTC的袭击造成了前所未有的环境暴露于雾化粉尘、气体和潜在致癌物。CH 被定义为在血细胞中获得体细胞突变，并且与吸烟和暴露于遗传毒性刺激有关。

附：英文原文

Title: High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster

Author: Jasra, Sakshi, Giricz, Orsi, Zeig-Owens, Rachel, Pradhan, Kith, Goldfarb, David G., Barreto-Galvez, Angelica, Silver, Alexander J., Chen, Jiahao, Sahu, Srabani, Gordon-Mitchell, Shanisha, Choudhary, Gaurav S., Aluri, Srinivas, Bhagat, Tushar D., Shastri, Aditi, Bejan, Cosmin A., Stockton, Shannon S., Spaulding, Travis P., Thiruthuvanathan, Victor, Goto, Hiroki, Gerhardt, Jeannine, Haider, Syed Hissam, Veerappan, Arul, Bartenstein, Matthias, Nwankwo, George, Landgren, Ola, Weiden, Michael D., Lekostaj, Jacqueline, Bender, Ryan, Fletcher, Frederick, Greenberger, Lee, Ebert, Benjamin L., Steidl, Ulrich, Will, Britta, Nolan, Anna, Madireddy, Advaitha, Savona, Michael R., Prezant, David J., Verma, Amit

Issue&Volume: 2022-03-07

Abstract: The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to aerosolized dust, gases and potential carcinogens. Clonal hematopoiesis (CH) is defined as the acquisition of somatic mutations in blood cells and is associated with smoking and exposure to genotoxic stimuli. Here we show that deep targeted sequencing of blood samples identified a significantly higher proportion of WTC-exposed first responders with CH (10%; 48 out of 481) when compared with non-WTC-exposed firefighters (6.7%; 17 out of 255; odds ratio, 3.14; 95% confidence interval, 1.64–6.03; P=0.0006) after controlling for age, sex and race/ethnicity. The frequency of somatic mutations in WTC-exposed first responders showed an age-related increase and predominantly affected DNMT3A, TET2 and other CH-associated genes. Exposure of lymphoblastoid cells to WTC particulate matter led to dysregulation of DNA replication at common fragile sites in vitro. Moreover, mice treated with WTC particulate matter developed an increased burden of mutations in hematopoietic stem and progenitor cell compartments. In summary, the high burden of CH in WTC-exposed first responders provides a rationale for enhanced screening and preventative efforts in this population.

DOI: 10.1038/s41591-022-01708-3

Source: https://www.nature.com/articles/s41591-022-01708-3

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex