High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.