Validation of a Nanopore-Based Cell-Free DNA Assay for Accurate Diagnosis of ALL

Grants and Contracts Details


ABSTRACT Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. The presence of minimal residual disease (MRD) after treatment or the spread of ALL into the central nervous system (CNS) is often associated with a worse prognosis. Clinicians must diagnose MRD or CNS disease as early as possible so that these children can receive intensified chemotherapy, immunotherapy, or bone marrow transplant to have the best chance at a cure. However, the current diagnostic technologies that rely on detecting ALL cells in the patient biopsy or fluids are not sensitive enough to diagnose MRD or CNS disease accurately when the leukemia burden is low. To resolve this issue, we have developed a new assay that uses nanopore sequencing technology to detect cell-free DNA (cfDNA) released by ALL cells into patient biofluids. All cancer cells release cfDNAs, which are small fragments of the cell’s genomic DNA. We were the first to apply cfDNA analysis to ALL, and our new assay is faster and less expensive than any MRD detection method currently available. Based on our preliminary work, we hypothesize that cell-free DNA will be a helpful diagnostic, monitoring, and prognostic biomarker in ALL. We are requesting funding from the COG Hematopoietic Malignancies Intergrated Translational Science Center to 1) Validate the sensitivity, specificity, and robustness of our nanopore-based cell-free DNA assay compared to current clinical diagnostic practices, and 2) Increase our cohort of patients to demonstrate an association between the presence of ALL-specific cfDNA and diagnosis of MRD and CNS disease. These validation and optimization steps will allow us to develop needed preliminary data and set up a strong team capable of moving our assay into clinical laboratories. Ultimately, we plan to build a clinical trial to use cfDNA monitoring to inform treatment plans. Providing clinicians with better tools to accurately diagnose children at high risk for poor outcomes in ALL will improve care and outcomes for these patients.
Effective start/end date3/1/232/29/24


  • Public Health Institute: $60,000.00


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.