A Rare BCR::SPECC1L::ABL1 Fusion in a Pediatric Chronic Myeloid Leukemia Patient.
This single pediatric CML case identified an atypical in-frame BCR::SPECC1L::ABL1 transcript retaining the ABL1 tyrosine kinase domain and used FISH and targeted NGS for diagnosis and imatinib monitoring when standard p210 RT-PCR was negative.
Open original publication →What the AI sees
This single pediatric CML case identified an atypical in-frame BCR::SPECC1L::ABL1 transcript retaining the ABL1 tyrosine kinase domain and used FISH and targeted NGS for diagnosis and imatinib monitoring when standard p210 RT-PCR was negative.
Research significance
The record shows that multimodal testing can detect and monitor this atypical fusion; it is plausible, but not demonstrated here, that retention of the ABL1 kinase domain could preserve sensitivity to ABL1-directed therapy such as imatinib.
Source abstract
BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm typically defined by BCR::ABL1 p210 fusions isoforms. OBSERVATIONS: An 8-year-old female CML patient harbored a typical t(9;22)(q34;11) Philadelphia chromosome and BCR::ABL1 fusion by conventional karyotyping and FISH but lacked BCR::ABL1 p210 fusion transcripts by RT-PCR. Targeted next-generation sequencing (NGS) revealed BCR::SPECC1L::ABL1 fusion transcripts predicted to encode an in-frame BCR-exon-8::SPECC1L-exon-4::ABL1-exon-2 fusion protein retaining the tyrosine kinase domain. FISH and NGS were used for therapeutic imatinib monitoring given this atypical isoform. CONCLUSIONS: This case highlights the role of multimodal molecular diagnostics to diagnose and monitor pediatric CML patients with atypical fusion isoforms.