ArticleBritish journal of haematology2026
Identification of GSE1 as a PAX5 fusion partner and characterization of PAX5 fusion signature in B-cell acute lymphoblastic leukaemia.
Article in British journal of haematology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
In B-cell acute lymphoblastic leukaemia (B-ALL), paired box 5 (PAX5) rearrangement (PAX5-r) represents a critical genetic driver. Here, we report the identification of an in-frame PAX5::GSE1 fusion gene in a patient with B-ALL. Functional characterization revealed that the PAX5::GSE1 protein localizes to the nucleus, promotes cell proliferation and suppresses wild-type PAX5 transcriptional activity. Notably, its transcript levels correlated with treatment response, supporting its utility as a minimal residual disease biomarker. By analysing 330 patients with PAX5-r B-ALL, we identified 76 distinct in-frame partner genes and delineated their breakpoint characteristics. Integrated multi-cohort transcriptomic analysis further revealed that PAX5-r induces a convergent expression profile relative to healthy individuals, characterized by dysregulation of the retinoblastoma transcriptional corepressor 1 (RB1) and p53 pathways and overexpression of nucleophosmin 1 (NPM1). These findings help to clarify core molecular mechanisms underlying PAX5-r-driven leukaemogenesis and highlight potential therapeutic vulnerabilities.
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