A new study in Nature Genetics explores the relationship between clonal hematopoiesis (CH) in cancer patients and their risk of developing a treatment-related blood cancer.
Therapy-related acute myeloid leukemia or myelodysplastic syndrome are rare secondary blood cancers that arise as a complication of cancer treatment. Recent studies have identified CH, mutations in the blood that occur with age and increase the risk for blood cancer, is frequently found in cancer patients and may explain why these therapy-related disorders develop.
Researchers from Memorial Sloan Kettering analyzed data from 24,000 patients with cancer being treated at their center and found one-third were positive for CH. They also found increased rates of CH in people who had already received treatment and were then able to draw connections between cancer therapies such as radiation therapy and certain chemotherapies and the presence of CH. Unlike CH changes found in the general population, CH mutations after cancer treatment occurred most frequently in genes which protect the genome from damage.
The MSK team followed up with a three-year study to explore the relationship between CH development and cancer therapy, enrolling more than 500 cancer patients who were screened for CH upon admission and then at a later point during treatment.
Patients with pre-existing CH whose blood carried mutations related to DNA damage were more likely to have mutations grow after receiving cancer therapies, when compared to those who did not receive treatment. For a subset of patients with CH who developed therapy-related blood cancers, their blood cells acquired further mutations and progressed to leukemia over time.
These findings may guide future cancer treatment guidelines by indicating whether some chemotherapy drugs are more likely to lead to therapy-related blood cancer development in patients with CH. The investigators also hope to use these findings to develop new methods of detecting CH-related blood cancers earlier, and potentially develop interventions to prevent CH from progressing to cancer.