The first responders who were exposed to high levels of airborne dust, gases, and potential cancer-causing substances at Ground Zero following the 9/11 attacks that destroyed the Twin Towers in New York may now be facing an increased risk of developing leukemia and exhibit a distinct spectrum of precancerous genetic changes, according to data presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition held in San Diego, CA. 1
Divij Verma, PhD, of Albert Einstein College of Medicine in the Bronx, New York, and colleagues obtained blood samples from 988 firefighters and emergency medical personnel who were at Ground Zero in the hours and days following the September attacks in 2001.
The researchers examined the responders’ genomes to determine how many had clonal hematopoiesis (CH) and how many of those with CH developed leukemia. On average, the blood samples were collected a decade after exposure. The investigators then compared the Ground Zero–exposed responders with 255 firefighters who had not been at the site but had occupational exposures to pollutants and potentially toxic substances and with 195 people from the general population who were not first responders and had not been at Ground Zero.
The researchers noted that those at Ground Zero were 3 times more likely to have genetic changes associated with an increased risk of blood cancer compared with other first responders. Those responders who were younger than age 60 who had worked at the site not only showed these genetic changes, which are rarely seen in older people, but the changes were unlike any previously seen in this condition, which commonly occur during normal aging.
Fourteen percent of the exposed first responders had CH, compared with 7% of firefighters and other people who had not been at Ground Zero. Even though DNMT3A and TET2 were the 2 most common mutated genes in Ground Zero–exposed responders, the subsequent spectrum of mutations was distinct in younger Ground Zero–exposed responders and included APC (6.6%), KMT2D (4.8%), ATM (4.8%), PIK3CA (4.2%), CREBBP (3.0%), BRCA2 (2.4%), ERBB4 (2.4%), and ARID1A (2.4%), which have not been reported in any previous CH studies.
Notably, in the firefighters and other first responders who had no Ground Zero exposure, the risk of having CH was the same as for people who were not first responders and had not been to the site. Among Ground Zero–exposed first responders with CH, the risk of developing leukemia was 3.7%, compared with 0.6% for those in the nonexposed comparison groups. Compared with exposed first responders without CH, those with CH had more genetic changes indicating an elevated risk for leukemia or another blood cancer, as well as increased levels of neutrophils and monocytes (types of white blood cells) and red cell width suggestive of greater inflammation.All Ground Zero–exposed first responders with CH are being contacted and invited to visit the hospital to identify any health problems as early as possible and initiate treatment, if necessary, Dr Verma said.
The researchers noted that while the gene for IL1RAP halted precancerous genetic changes in mice, no studies have yet been done to show whether this strategy will work in people. They noted that IL1RAP is a potentially important target, as it inhibits signaling from several mediators of inflammation. Targeting IL1RAP holds significant potential for reducing inflammation and combating inflammation-driven malignancies, he said.This study was funded by grants from the Centers for Disease Control and Prevention and the National Institutes of Health.
Reference
Verma D, Owens RZ, Goldfarb DG, et al. Elevated clonal hematopoiesis in environmentally exposed responders has distinct age-related patterns and relies on IL1RAP for clonal expansion. Presented at: 66th ASH Annual Meeting and Exposition. December 7-10, 2024; San Diego, CA. Abstract 943.