Studies on clonal hematopoiesis in the 911 WTC first responders
Amit Verma
MBBSAlbert Einstein College of Medicine
Project Term: June 1, 2022 - TBD
The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to WTC aerosolized dust and gases that contained known and suspected carcinogens including polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polychlorinated furans, dioxins and asbestos. Studies from Dr. Verma's group and others have reported an excess of cancer cases in the WTC-exposed Fire Department of the City of New York (FDNY) firefighters, including a trend towards higher incidence of multiple myeloma and leukemias. He now will be deep sequencing a large group of WTC-exposed firefighters to look for clonal hematopoiesis (CH) which is an acquisition of leukemia associated mutations associated with increases in the risk of hematologic cancer.
The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to WTC aerosolized dust and gases that contained known and suspected carcinogens including polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polychlorinated furans, dioxins and asbestos. Studies from Dr. Verma's group and others have reported an excess of cancer cases in the WTC-exposed Fire Department of the City of New York (FDNY) firefighters, including a trend towards higher incidence of multiple myeloma and leukemias.
They have conducted deep targeted genome sequencing of a small initial group of WTC exposed firefighters and non-WTC exposed firefighter controls looking for clonal hematopoiesis (CH). CH is acquisition of leukemia associated somatic mutations associated with increases in the risk of hematologic cancer as well as all-cause mortality. They observed a higher incidence of CH associated mutations in WTC exposed firefighters when compared to controls.
The group now proposes to comprehensively determine the prevalence of CH in a large cohort of WTC exposed first responders and study the molecular and cellular mechanisms of damage caused by WTC particulate matter. The funded project will be focusing on genomic assays including sequencing of blood samples from first responders. These funded studies will contribute to determining the prevalence of CH mutations using deep targeted sequencing in a larger group of WTC exposed firefighter and 2 groups of control samples (non-WTC firefighters and non-firefighter age matched controls).
Mutations will be correlated with clinical variables such as level of WTC exposure, age, serial blood counts, smoking history, and other clinical characteristics. Early detection of CH mutations will enable clinical evaluation of first responder firefighters and enable potential disease altering therapeutic interventions.