A novel BCR-ABL1 fusion gene identified by next-generation sequencing in chronic myeloid leukemia

Background BCR-ABL1 fusion proteins contain constitutively active tyrosine kinases that are potential candidates for targeted therapy with tyrosine kinase inhibitors such as imatinib in chronic myeloid leukemia (CML). However, uncharacterized BCR-ABL1 fusion genes can be missed by quantitative RT-PCR (qRT-PCR)-based routine screening methods, causing adverse effect on drug selection and treatment outcome. Case presentation In this study, we demonstrated that the next-generation sequencing (NGS) can be employed to overcome this obstacle. Through NGS, we identified a novel BCR-ABL1 fusion gene with breakpoints in the BCR intron 14 and the ABL1 intron 2, respectively, in a rare case of CML. Its mRNA with an e14a3 junction was then detected using customized RT-PCR followed by Sanger sequencing. Subsequently, the patient received targeted medicine imatinib initially at 400 mg/day, and later 300 mg/day due to intolerance reactions. With this personalized treatment, the patient’s condition was significantly improved. Interestingly, this novel fusion gene encodes a fusion protein containing a compromised SH3 domain, which is usually intact in the majority of CML cases, suggesting that dysfunctional SH3 domain may be associated with altered drug response and unique clinicopathological manifestations observed in this patient. Conclusion We identified a novel BCR-ABL1 fusion gene using NGS in a rare case of CML while routine laboratory procedures were challenged, demonstrating the power of NGS as a diagnostic tool for detecting novel genetic mutations. Moreover, our new finding regarding the novel fusion variant will provide useful insights to improve the spectrum of the genomic abnormalities recognizable by routine molecular screening.