ArticleBritish journal of cancer2025
Innovative rapid screening for complex BCR-ABL1 kinase domain mutations in TKI-treated leukaemia patients.
Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Intrinsic cellular resistance to BCR::ABL1 inhibitors.Haematologica · 2026Review
- A mouse-adapted Yezo virus model for antiviral testing in immunocompetent mice.Nature communications · 2026Article
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Authors and funding
10 authors.
Funding
Abstract
backgroundScreening for BCR-ABL1 kinase domain (KD) mutations is routinely implemented in cases of treatment failure for chronic myeloid leukaemia and Philadelphia-positive acute lymphoblastic leukaemia. However, timely deciphering their clonal relationship via mutation profiling that requires identification of mutation types, quantification of mutant abundance, and differentiation between compound and polyclonal mutations (CMs and PMs), remains difficult during therapy.
methodsHerein, we established a protocol that identified mutation types and further distinguished clonal relationships by combining mini-sequencing of MeltArray with allele segregation of droplet digital PCR (ddPCR).
resultsThe analysis showed that 78 samples (18.93%) were mutant, of which 50 (64.1%) harboured single mutations, and 28 (35.9%) contained multiple mutations, including double-, triple-, quadruple- and hepta-mutants. These results agreed with NGS, except one sample with F317L and L324Q mutations, where L324Q was beyond MeltArray's scope. Among cases containing multiple mutations, 85.71% were PMs, 10.71% were CMs, and 3.57% were mixed CMs and PMs. Retrospective analysis revealed that clonal relationships in BCR-ABL1 KD mutations were highly dynamic during therapy.
conclusionsThe MeltArray-ddPCR protocol enables dynamic profiling of BCR-ABL1 KD mutations to determine clonal status, improving prediction of drug susceptibility and leukaemia outcomes. In this study, we performed a retrospective analysis of 539 samples from 365 leukaemia patients. We developed a comprehensive BCR-ABL1 kinase domain mutation screening protocol that includes pre-amplification, mutation screening, and differentiation between compound mutations (CMs) and polyclonal mutations (PMs). By integrating MeltArray and ddPCR technologies, this protocol enables dynamic monitoring of changes in mutation levels and clonal evolution. It also offers companion diagnostics based on mutational profiles to guide precision therapy for leukaemia patients.
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