title: A novel BCR-ABL1 fusion gene identified by next-generation sequencing in chronic myeloid leukemia.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450000 China.|Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, Henan 450000 China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Lyu
authors.affiliation: Department of Hematology, the Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, Henan 450000 China.
authors.forename: Jingke
authors.initials: J
authors.lastname: Yang
authors.affiliation: Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, Henan 450000 China.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, Henan 450000 China.
authors.forename: Jieying
authors.initials: J
authors.lastname: Hu
authors.affiliation: Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, Henan 450000 China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, Henan 450000 China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, Henan 450000 China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450000 China.
authors.forename: Bingshan
authors.initials: B
authors.lastname: Liu
authors.affiliation: Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, Henan 450000 China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Hematology, the Affiliated Cancer Hospital of Zhengzhou University; Henan Cancer Hospital, Zhengzhou, Henan 450000 China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Song
keywords: BCR-ABL1; Chronic myeloid leukemia; Imatinib; Next-generation sequencing; SH3 domain; Tyrosine kinase