Acute myeloid leukemia (AML) is a challenging malignancy to treat in pediatric patients. Disease monitoring following treatment involves quantifying small numbers of leukemic cells that remain in the patient using minimal residual disease (MRD) assays. Roughly one-third of AML cases do not harbor markers amenable to the gold-standard methods for assessing MRD and predicting relapse risk in AML. Sequencing studies have demonstrated that virtually all AML cases contain leukemia-specific single-nucleotide mutations, but these assays lack sensitivity for use as a clinical tool. Error-corrected next-generation sequencing (ECS), employed by the Druley lab, enables the detection of rare leukemic cells harboring these mutations.
This project will enable ECS targeting dozens of genes to assess MRD in nearly all pediatric AML cases with comparable accuracy to conventional methods, leading to improved genetic diagnostics for pediatric cancer patients.
The aims of this proposal are to:
1. Extend ECS to test multiple different recurrently mutated genes in AML.
2. Apply ECS-MRD testing to approximately 150 remission pediatric AML samples with MRD status and correlate MRD status with outcome.
3. Validate the criteria established in Aim 2 using approximately 100 pediatric AML remission samples with diagnostic genome sequencing and MRD status.
This new assay will extend the life-saving capability of MRD to virtually every pediatric AML patient.