Clinical Scorecard: Targeted Adaptive Sampling Long-Read Sequencing for Genome Profiling in Childhood Leukemia
At a Glance
Category
Detail
Condition
Childhood leukemia including AML, B-ALL, and T-ALL
Key Mechanisms
Targeted adaptive sampling long-read sequencing (TAS-LRS) enables comprehensive detection of structural variations (SVs), copy number variations (CNVs), and single-nucleotide variants (SNVs) with shorter turnaround time and haplotype-aware variant calling
Target Population
Children with leukemia requiring genome profiling for diagnosis, risk stratification, and therapeutic target identification
TAS-LRS successfully performed tumor/normal-paired genome profiling in 28 pediatric leukemia patients within approximately 72 hours from library preparation to results.
TAS-LRS detected 498 SNVs, 35 small indels, and 632 SVs, including driver alterations and genomic subtypes consistent with or beyond conventional clinical testing.
TAS-LRS demonstrated superior detection of SVs and CNVs, including cryptic fusions and large deletions overlooked by standard clinical tests and short-read sequencing.
Guideline-Based Recommendations
Diagnosis
Use TAS-LRS for comprehensive genome profiling in pediatric leukemia to identify genomic subtypes and driver alterations.
Perform tumor/normal-paired analysis to improve variant calling accuracy and reduce false positives from germline variants or sequencing errors.
Management
Incorporate TAS-LRS findings into leukemia classification and risk stratification to guide targeted therapy decisions.
Utilize TAS-LRS to detect fusion breakpoints for fusion-based minimal residual disease (MRD) assays.
Monitoring & Follow-up
Apply TAS-LRS for monitoring fusion breakpoints and genomic alterations relevant to disease progression and treatment response.
Risks
Tumor-only analysis may yield false positives due to germline variants or sequencing errors; paired normal analysis is recommended to mitigate this.
Some driver variants may be missed by tumor/normal-paired analysis due to quality filtering; careful review of variant calls is necessary.
Patient & Prescribing Data
Pediatric patients with acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), and T-cell acute lymphoblastic leukemia (T-ALL)
Genomic profiling by TAS-LRS enables precise diagnosis and identification of therapeutic targets, facilitating personalized treatment strategies.
Clinical Best Practices
Perform tumor/normal-paired TAS-LRS to maximize accuracy in variant detection and subtype classification.
Include a broad panel of hematologic malignancy-associated genes (466 genes) for comprehensive profiling.
Use complementary approaches such as single breakend SV detection and de novo assembly to detect complex rearrangements like DUX4.
Compare TAS-LRS results with conventional clinical tests and short-read WGS to validate findings and ensure comprehensive variant detection.
Leverage TAS-LRS for additional applications such as NUDT15 diplotyping and fusion breakpoint detection for MRD.
