Detection of BCR::ABL1-like ALL using RT-PCR, a targeted RNA panel, and RNA sequencing.
Hanwool Cho1, Chae Yeon Lee2, Jin Jung3
1Department of Laboratory Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Leukemia Research
|April 24, 2026
Summary
Whole-transcriptome RNA sequencing (WTS) offers the most comprehensive detection of genetic alterations in BCR::ABL1-like acute lymphoblastic leukemia (ALL). This approach optimizes molecular classification and guides targeted therapy decisions for this high-risk subtype.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- B-lymphoblastic leukemia with BCR::ABL1-like features (BCR::ABL1-like ALL) is a high-risk subtype characterized by kinase-activating genetic alterations.
- Accurate detection of these genetic lesions is critical for molecular classification and guiding targeted therapies.
Purpose of the Study:
- To evaluate and optimize RNA-based diagnostic platforms for detecting kinase-activating lesions in BCR::ABL1-like ALL.
- To establish an optimal diagnostic strategy for molecular classification and targeted therapy selection.
Main Methods:
- Comparative analysis of multiplex RT-PCR, targeted RNA panels, and whole-transcriptome RNA sequencing (WTS) in a cohort of B-ALL patients.
- Utilized DRAGEN and Arriba fusion workflows for WTS data analysis and ALLCatchR for transcriptome classification.
Main Results:
- Whole-transcriptome RNA sequencing (WTS) identified the highest number of genetic lesions (85%), including known and novel rearrangements, when combining DRAGEN and Arriba.
- Multiplex RT-PCR detected 20% of events, while targeted RNA panels identified 45% but showed panel-dependent limitations and misclassifications.
- ALLCatchR classified 78% of analyzable cases to the BCR::ABL1-like subtype, providing resolution beyond structural variant identification.
Conclusions:
- Whole-transcriptome RNA sequencing (WTS), coupled with robust fusion pipelines and transcriptomic classification, provides the most comprehensive assessment of kinase-activating lesions in BCR::ABL1-like ALL.
- An optimized strategy prioritizing WTS for cases not fully resolved by FISH or targeted RNA panels enables accurate molecular classification and guides targeted therapy.
