A complex mutational signature generated by cytarabine resistance (CR)
This study aims to uncover the genetic mechanisms underlying chemotherapy resistance in relapsed T-cell acute lymphoblastic leukemia (T-ALL). By using a genetically modified pre-leukemic cell model with increased mutational activity, the research identifies unique mutational signatures and specific gene disruptions, particularly in the DCK gene, that contribute to resistance against cytarabine, a commonly used chemotherapeutic. The study found distinct patterns of DNA mutations associated with cell proliferation, DNA repair deficiency, and TP53 mutations, revealing how chemotherapy resistance evolves during relapse. These insights significantly enhance our understanding of how drug-resistant leukemia develops and may guide the creation of more targeted therapies in the future for patients with T-ALL. This research holds promise for advancing precision medicine strategies to improve outcomes for those facing relapsed leukemia