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

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 transfecti...

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Main Authors: Tao Liu, Yang Wang, Xi-Zhou An, Jiaqi Liu, Yuqin Wu, Yan Xiang, Yong-Jie Zhang, Lan Huang, Jia-Cheng Li, Yu-Zhuo-Pu Li, Jie Yu
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86865-4
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Summary: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.
ISSN:2045-2322