Identification of a novel TOP2B::AFF2 fusion gene in B-cell acute lymphoblastic leukemia

Sci Rep. 2025 Jan 25;15(1):3280. doi: 10.1038/s41598-025-86865-4.

Abstract

Genetic alterations play a pivotal role in leukemic clonal transformation, significantly influencing disease pathogenesis and clinical outcomes. Here, we report a novel fusion gene and investigate its pathogenic role in acute lymphoblastic leukemia (ALL). We engineer a transposon transfection system expressing the TOP2B::AFF2 transcript and introduce it into Ba/F3 cells. Functional studies, including proliferation, cell cycle, and apoptosis assays, were conducted to assess the fusion gene's impact. In vitro assays reveal that the TOP2B::AFF2 fusion significantly enhances Ba/F3 cell proliferation and G1/S phase transition while suppressing differentiation and apoptosis. This study identifies TOP2B::AFF2 as a potential oncogenic driver. However, further validation through in vivo studies are warranted to fully elucidate the fusion gene's role in leukemogenesis.

Keywords: Acute lymphoblastic leukemia; Differentiation; Fusion gene; TOP2B.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Proliferation* / genetics
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Mice
  • Oncogene Proteins, Fusion* / genetics
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology

Substances

  • Oncogene Proteins, Fusion
  • DNA Topoisomerases, Type II
  • Poly-ADP-Ribose Binding Proteins
  • DNA-Binding Proteins