Detection of a cryptic NUP214/ABL1 gene fusion by mate-pair sequencing (MPseq) in a newly diagnosed case of pediatric T-lymphoblastic leukemia

Cold Spring Harb Mol Case Stud. 2019 Apr 1;5(2):a003533. doi: 10.1101/mcs.a003533. Print 2019 Apr.

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm involving the bone marrow and blood that accounts for ∼15% of childhood and 25% of adult ALL. Whereas multiple, recurrent genetic abnormalities have been described in T-ALL, their clinical significance is unclear or controversial. Importantly, ABL1 rearrangements, most commonly described in BCR/ABL1-positive B-ALL and BCR-ABL1-like B-ALL, have been observed in T-ALL and may respond to tyrosine kinase inhibitor (TKI) therapy. We describe a newly diagnosed case of pediatric T-ALL with a fluorescence in situ hybridization abnormality suggesting a partial ABL1 deletion by a BCR/ABL1 dual-color dual-fusion probe but that demonstrated a normal result using an ABL1 break-apart probe. Mate-pair sequencing (MPseq), a next-generation sequencing (NGS)-based technology utilized to detect copy number and structural abnormalities with high resolution and precision throughout the genome, was performed and revealed a NUP214/ABL1 gene fusion that has been demonstrated to be sensitive to TKI therapy. This case demonstrates the power of MPseq to resolve chromosomal abnormalities unappreciable by traditional cytogenetic methodologies and highlights the clinical value of this novel NGS-based technology.

Keywords: T-cell acute lymphoblastic leukemias.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child, Preschool
  • High-Throughput Nucleotide Sequencing
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Nuclear Pore Complex Proteins / genetics*
  • Oncogene Proteins, Fusion / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Proto-Oncogene Proteins c-abl / genetics*
  • Sequence Analysis, DNA
  • Treatment Outcome

Substances

  • NUP214 protein, human
  • Nuclear Pore Complex Proteins
  • Oncogene Proteins, Fusion
  • ABL1 protein, human
  • Proto-Oncogene Proteins c-abl