Clonal hematopoiesis occurs more often in pediatric cancer survivors; is associated with exposures to alkylating agents, radiation, bleomycin
By Elana Gotkine HealthDay Reporter
FRIDAY, Feb. 10, 2023 (HealthDay News) — Clonal hematopoiesis (CH) occurs more often in pediatric cancer survivors than community controls, according to a study published online Feb. 8 in Cancer Discovery.
Kohei Hagiwara, Ph.D., from St. Jude Children’s Research Hospital in Memphis, Tennessee, and colleagues examined CH in 2,860 long-term survivors of pediatric cancer, who were followed for a median of 23.5 years. Deep sequencing was performed in 39 CH-related genes.
The researchers identified mutations in 15 percent of survivors compared with 8.5 percent of 324 community controls. In survivors, CH was associated with exposures to alkylating agents, radiation, and bleomycin. Significant enrichment in STAT3 and in TP53 was seen with therapy-related CH. STAT3 mutations were mainly present in T cells and contributed to SBS25, a mutational signature associated with exposure to procarbazine. On serial tracking of samples, larger clone size was identified as a predictor of future expansion of age-related CH clones, while therapy-related CH remained stable for decades following treatment.
“The data are telling us that CH mutations are important biomarkers that have potential clinical implications for risk of adverse long-term outcomes among the growing population of survivors of childhood cancer,” a coauthor said in a statement. “The research methods applied provide new insights and a new level of research on clonal hematopoiesis that will inform future studies.”
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