1. Feasibility of monitoring peripheral blood to detect emerging clones in children with acute lymphoblastic leukemia
- Author
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Nikki A. Evensen, Daniel P. Newman, Julia Meyer, Jacob Nersting, Kjeld Schmiegelow, Sonali Narang, Xiaotu Ma, Jason Saliba, and William L. Carroll
- Subjects
Somatic cell ,Lymphoblastic Leukemia ,Drug resistance ,Somatic evolution in cancer ,Polymerase Chain Reaction ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Maintenance therapy ,law ,Biomarkers, Tumor ,Medicine ,Humans ,Child ,Gene ,Polymerase chain reaction ,business.industry ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,Combined Modality Therapy ,Peripheral blood ,Clone Cells ,Oncology ,030220 oncology & carcinogenesis ,Case-Control Studies ,Pediatrics, Perinatology and Child Health ,Immunology ,Mutation ,Feasibility Studies ,Female ,Neoplasm Recurrence, Local ,business ,030215 immunology ,Follow-Up Studies - Abstract
Relapse-enriched somatic variants drive drug resistance in childhood acute lymphoblastic leukemia. We used digital droplet-based polymerase chain reaction to establish whether relapse-enriched mutations in emerging subclones could be detected in peripheral blood samples before frank relapse. Although limitations in sensitivity for some probes hindered detection of certain variants, we successfully detected variants in NT5C2 and PRPS1 at a fractional abundance of 0.005% to 0.3%, 41 to 116 days before relapse. As mutations in both these genes confer resistance to thiopurines, early detection protocols using peripheral blood could be implemented to preemptively alter maintenance therapy to extinguish resistant clones before overt relapse.
- Published
- 2020