In blood of patients treated for other cancers, researchers find genetic precursors of leukemia

In a study presented at the American Society of Hematology Annual Meeting in San Diego, Catherine C. Coombs, MD, MS, and colleagues reported that nearly a quarter of patients heavily treated for other cancers had mutations in their white blood cells, and that the majority of those mutations were leukemia-linked.

In blood of patients treated for other cancers, researchers find genetic precursors of leukemia click to enlarge Catherine C. Coombs, MD, MS, is an assistant professor in the UNC School of Medicine.

Genetic mutations found in the blood of patients heavily treated for other cancers led to an increased risk for developing blood cancer later on, researchers found in a new study.

Researchers analyzed mutations in the blood of patients who had already been heavily treated for non-hematologic cancers in a study presented at the American Society of Hematology Annual Meeting in San Diego. They found that nearly a quarter of patients in the study had mutations in their white blood cells, and that the majority of those mutations were leukemia-linked. For a subset of patients with certain leukemia-linked mutations, patients had a higher risk for developing blood cancers later, and had risk of lower overall survival.

“This study shows that we can identify leukemia-associated mutations in a cohort of extensively pre-treated cancer patients,” said Catherine C. Coombs, MD, MS, an assistant professor in the UNC School of Medicine. “These mutations have previously been shown to occur in non-cancer populations, and are a known consequence of aging. When looking at the impact of these mutations on the cancer population, they’re associated with inferior overall survival, and a risk for developing subsequent hematologic cancers though that absolute risk is very low.”

For the study, researchers sequenced the genes of cells in the blood and from tumors in more than 7,200 patients with non-hematologic cancers at Memorial Sloan Kettering Cancer Center. Coombs was a fellow at Memorial Sloan Kettering prior to her role at the UNC School of Medicine.

Coombs and her colleagues found acquired mutations in white blood cells and not in tumors -- a phenomenon known as clonal hematopoiesis -- in 23.4 percent of patients’ blood samples. The presence of these leukemia-linked mutations was associated with increased age, prior radiation therapy, tobacco use and increased age. However, they were not linked with prior treatment with chemotherapy.

They also found that the presence of a subset of leukemia-driving mutations led to an increased risk of subsequent blood cancer. Coombs said the implication of this finding is that the presence of these mutations could help predict risk for developing a later blood cancer, and could play a role in risk-benefit discussion for patients for whom treatment is optional, such as for patients who have early-stage cancers.

Their findings could also have implications for the accuracy of cancer blood tests or tests in solid tumors where blood may contaminate samples, Coombs also said. The finding of cancer-linked mutations in the blood alone could support arguments for paired sequencing of both the blood and tumors to correctly identify mutations involved in cancer.

“Knowing that these blood-associated mutations are present would be a significant confounding variable when interpreting tumor-only genomic assays,” she said. “Some scientists sequence the tumor, and not the blood. This shows there could be the potential for miscalling tumor-associated mutations based on blood contaminating a tumor.”

In addition to Coombs, other authors include: Ahmet Zehir, Sean Devlin, Ashwin Kishtagari, David M. Hyman, David Solit, Mark Robson, Jose Baselga, Maria Arcila, Martin S. Tallman, Ross L. Levine, and Michael Berger.