Chemotherapy drives changes to the genome and clonal architecture of blood stem cells that may increase risk of secondary malignancies
MD Anderson Research Highlight July 01, 2025
Hematopoietic stem and progenitor cells (HSPCs) – a main source of blood cell production – can accumulate DNA mutations over time, which can be influenced by various external stressors. However, it is unclear how chemotherapy in patients with cancer affects mutations in their normal HSPCs. To provide insights, researchers led by Koichi Takahashi, M.D., Ph.D., conducted whole-genome sequencing on 1,276 single-cell-derived HSPCs from 10 previously-treated patients with multiple myeloma. They characterized the effects of several chemotherapy drugs, including melphalan, which increased the risk of developing certain mutations. The researchers also found that chemotherapy accelerated the remodeling of HSPCs, leading to a reduction in their clonal diversity. This research suggests that chemotherapy can accelerate the development of mutations that could increase the risk for later leukemia, which may help researchers to better understand these risks and develop interventions to prevent chemotherapy-related secondary cancers. Learn more in Nature Genetics.
Our study uncovers the hidden long-term effects of chemotherapy on normal hematopoietic stem cells, revealing accelerated clonal aging and the emergence of high-risk hematopoietic clones that predispose to leukemic transformation. These are findings that have important clinical implications for early detection and prevention of therapy-related myeloid neoplasms.