Real-time genomic characterization of pediatric acute leukemia using adaptive sampling

Abstract

Acute lymphoblastic leukemia (ALL) is an aggressive stem cell disorder characterized by the rapid proliferation of immature white blood cells, which often contain chromosomal abnormalities and gene fusions. Identifying an appropriate treatment regimen depends on precise clinical diagnosis, typically derived from a combination of multiple time-consuming and costly techniques such as fluorescence in situ hybridization (FISH), flow cytometry, cytogenetics, targeted PCR, and microarrays. Yet, the current standard of care remains inaccessible in many healthcare settings and leads to delays in treatment, which jeopardize patient outcomes. We investigated the feasibility of using nanopore-based sequencing with adaptive sampling to characterize chromosomal abnormalities characteristic of ALL rapidly and affordably. We performed whole-genome sequencing (WGS) on DNA from peripheral blood mononuclear cell (PBMC) samples from 24 pediatric acute leukemia patients with a diversity of clinically diagnosed subtypes. We demonstrate the consistent characterization of known (clinically relevant) gross karyotype abnormalities and gene fusions from WGS with and without adaptive sampling at moderate sequencing depth in all 24 samples. WGS using nanopore sequencing with adaptive sampling has the future potential to provide clinical classification of ALL specimens while greatly reducing the cost and time to treatment. Further refinement of this methodology is necessary to determine robust limits of detection and demonstrate the utility of this approach as a primary low-cost diagnostic tool applicable across a wide range of cancer treatment settings.

Biography

Julie Geyer is a post-doctoral researcher at The University of North Carolina at Chapel Hill in the School of Medicine studying cancer genomics, specifically the genetic underpinnings of pediatric B-cell acute lymphoblastic leukemia (B-ALL). She is part of a multidisciplinary team of academic researchers and clinicians seeking to develop an accessible, reliable, and fast diagnostic tool for pediatric cancer.