Agent Orange and Bone Marrow Cancer: Novel Research Links Exposure to Aggressive MDS

More than 50 years after its use in Vietnam, a national study published in Blood Advances highlights the genetic changes linking Agent Orange exposure to myelodysplastic syndromes (MDS), a group of bone marrow cancers that can progress to acute leukemia. These findings offer crucial insight into why some veterans develop more severe bone marrow cancers and may help secure service-connected care for those affected.

Understanding the Link Between Agent Orange and MDS

The research, led by Mikkael A. Sekeres, M.D., chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, builds upon findings presented at the 2025 American Society of Hematology (ASH) Annual Meeting. Dr. Sekeres explained, “In the initial work presented at ASH, we had seen an association between Agent Orange exposure and developing MDS. Now we are describing how the disease biology looks different in this exposed group.”

Agent Orange, an herbicide used by the U.S. Military during the Vietnam War to defoliate forests and destroy crops, often contained dioxin, a highly toxic chemical that disrupts cellular processes. Approximately 2.6 million U.S. Service members were potentially exposed. While Agent Orange has already been linked to several cancers, including certain lymphomas and multiple myeloma, the connection to MDS was previously less clear.

Genetic Changes and Disease Progression

MDS typically develops slowly and is diagnosed later in life, often in individuals in their 70s. The accumulation of genetic mutations in blood-forming stem cells over time leads to the bone marrow’s inability to produce healthy blood cells. This research, utilizing data from the National Heart, Lung, and Blood Institute’s MDS Natural History Study, reveals a distinct pattern in veterans exposed to Agent Orange.

Among 2,115 patients enrolled in the study, 130 (6.1%) reported Agent Orange exposure, with 96% of those being men. Exposed patients were 54% more likely to receive an MDS or related precursor diagnosis compared to unexposed patients. Veterans with Agent Orange exposure were diagnosed with MDS, on average, several years earlier than those without exposure.

During the first two years post-diagnosis, exposed patients exhibited an approximately 80% higher likelihood of disease progression to more severe MDS or acute leukemia. However, overall survival rates remained similar between the two groups throughout the study period.

The Blood Advances paper details specific genetic changes associated with this pattern. Researchers found that veterans exposed to Agent Orange were more than twice as likely to exhibit high-risk chromosome abnormalities, indicating a more aggressive disease course. Specific mutations – including TET2, SRSF2, U2AF1, ZRSR2 and KRAS – were also more frequently observed in exposed patients, impacting how cells process genetic instructions and maintain healthy bone marrow function.

Dr. Sekeres noted, “It’s not a single event that leads to this cancer. You acquire one mutation, then another. Over years or decades, those changes build. What we’re seeing is that Agent Orange added a mutation—and that mutation sets patients on the road to cancer 50 years later.”

Disproportionate Impact on Black Veterans

The study also revealed a concerning trend: patients reporting Agent Orange exposure were disproportionately Black men, a rate higher than their representation in Vietnam service demographics. Approximately one in five exposed male patients in the registry was Black—more than double the rate observed among unexposed men. Even after adjusting for other factors, Black veterans were nearly three times more likely to report Agent Orange exposure.

Dr. Sekeres acknowledged, “The numbers were out of proportion to the percentage of Blacks who served in Vietnam. Blacks were possibly placed in vulnerable positions while serving and, more exposed to toxins like Agent Orange.”

The Push for Service Connection and Veteran Care

Following the presentation of these findings at the ASH meeting, Dr. Sekeres received an influx of inquiries from veterans seeking clarity on whether their illnesses could be linked to their military service and whether they were eligible for service-connected healthcare.

“We have aging veterans developing MDS who are being told by the Veterans Association that they can’t get their health care covered to the extent they need due to the fact that there hasn’t been an official association made,” Dr. Sekeres stated.

This new research provides the strongest data to date linking Agent Orange exposure to distinct genetic changes and more aggressive disease. Dr. Sekeres expressed hope that the Institute of Medicine will recognize Agent Orange exposure as a risk factor for MDS, ultimately ensuring that affected veterans receive the service-connected care they deserve.