A Rare BCR::SPECC1L::ABL1 Fusion in a Pediatric Chronic Myeloid Leukemia Patient

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.