High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster.
High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster.
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DOI：
10.1038/s41591-022-01708-3
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发表时间：
2022-03
期刊：
影响因子：
82.9
通讯作者：
Verma, Amit
中科院分区：
文献类型：
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作者：
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
对世界贸易中心(WTC)的恐怖袭击在环境中造成了前所未有的雾化粉尘、气体和潜在致癌物的暴露。克隆性造血(CH)被定义为获得血细胞的体细胞突变，并与吸烟和暴露于遗传毒性刺激有关。在这里，我们显示，在控制了年龄、性别和种族后，血液样本的深度靶向测序发现接触世贸中心的急救人员患有CH的比例(10%；48/481)明显高于未接触世贸中心的消防员(6.7%；17/255；OR=3.14(95%CI：1.64-6.03，p值=0.0006)。在WTC暴露的第一反应者中，体细胞突变的频率显示出与年龄相关的增加，并且主要影响DNMT3A、TET2和其他CH相关基因。在体外，淋巴母细胞暴露于WTC颗粒物(WTC-PM)导致常见脆弱部位的DNA复制失调。此外，接受WTC-PM治疗的小鼠在造血干细胞室和祖细胞室发生了更多的突变。总之，暴露于WTC的急救者的高负担为在这一人群中加强筛查和预防工作提供了理由。世贸中心灾难的急救人员暴露在含有潜在致癌物质的颗粒物中，血细胞体细胞突变的负担很大，增加了他们患癌症和其他疾病的风险，并突显了加强对这些人进行健康筛查的必要性。
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%; 48/481) when compared to non-WTC-exposed firefighters (6.7%; 17/255; OR=3.14 (95% CI:1.64–6.03, p-value=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 (WTC-PM) led to dysregulation of DNA replication at common fragile sites in vitro. Moreover, mice treated with WTC-PM 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. First responders to the World Trade Center disaster, who were exposed to particulate matter containing potential carcinogens, have a high burden of somatic mutations in blood cells, raising their risk for cancer and other diseases and highlighting the need for enhanced health screening of these individuals.
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影响因子：
64.8
作者：
Bick AG;Weinstock JS;Nandakumar SK;Fulco CP;Bao EL;Zekavat SM;Szeto MD;Liao X;Leventhal MJ;Nasser J;Chang K;Laurie C;Burugula BB;Gibson CJ;Lin AE;Taub MA;Aguet F;Ardlie K;Mitchell BD;Barnes KC;Moscati A;Fornage M;Redline S;Psaty BM;Silverman EK;Weiss ST;Palmer ND;Vasan RS;Burchard EG;Kardia SLR;He J;Kaplan RC;Smith NL;Arnett DK;Schwartz DA;Correa A;de Andrade M;Guo X;Konkle BA;Custer B;Peralta JM;Gui H;Meyers DA;McGarvey ST;Chen IY;Shoemaker MB;Peyser PA;Broome JG;Gogarten SM;Wang FF;Wong Q;Montasser ME;Daya M;Kenny EE;North KE;Launer LJ;Cade BE;Bis JC;Cho MH;Lasky-Su J;Bowden DW;Cupples LA;Mak ACY;Becker LC;Smith JA;Kelly TN;Aslibekyan S;Heckbert SR;Tiwari HK;Yang IV;Heit JA;Lubitz SA;Johnsen JM;Curran JE;Wenzel SE;Weeks DE;Rao DC;Darbar D;Moon JY;Tracy RP;Buth EJ;Rafaels N;Loos RJF;Durda P;Liu Y;Hou L;Lee J;Kachroo P;Freedman BI;Levy D;Bielak LF;Hixson JE;Floyd JS;Whitsel EA;Ellinor PT;Irvin MR;Fingerlin TE;Raffield LM;Armasu SM;Wheeler MM;Sabino EC;Blangero J;Williams LK;Levy BD;Sheu WH;Roden DM;Boerwinkle E;Manson JE;Mathias RA;Desai P;Taylor KD;Johnson AD;NHLBI Trans-Omics for Precision Medicine Consortium;Auer PL;Kooperberg C;Laurie CC;Blackwell TW;Smith AV;Zhao H;Lange E;Lange L;Rich SS;Rotter JI;Wilson JG;Scheet P;Kitzman JO;Lander ES;Engreitz JM;Ebert BL;Reiner AP;Jaiswal S;Abecasis G;Sankaran VG;Kathiresan S;Natarajan P
通讯作者：
Natarajan P
影响因子：
28.4
作者：
Landgren O;Zeig-Owens R;Giricz O;Goldfarb D;Murata K;Thoren K;Ramanathan L;Hultcrantz M;Dogan A;Nwankwo G;Steidl U;Pradhan K;Hall CB;Cohen HW;Jaber N;Schwartz T;Crowley L;Crane M;Irby S;Webber MP;Verma A;Prezant DJ
通讯作者：
Prezant DJ
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
10.4
作者：
McGee JK;Chen LC;Cohen MD;Chee GR;Prophete CM;Haykal-Coates N;Wasson SJ;Conner TL;Costa DL;Gavett SH
通讯作者：
Gavett SH
DOI：
10.1084/jem.20201544
发表时间：
2021-07-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Trowbridge JJ;Starczynowski DT
通讯作者：
Starczynowski DT