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<p>T-cell receptor (<i>TCR</i>) loci undergo complex <i>V(D)J</i> rearrangements during T-cell maturation. However, errors in this process can cause <i>TCR</i> promoters and enhancers to aberrantly fuse with oncogenes, leading to their overexpression and the development of T-cell acute lymphoblastic leukemia (T-ALL). Unexpectedly, in a retrospective study of 97 pediatric B-ALL cases, all diagnosed according to WHO criteria at a single institution, we identified a subgroup of B-ALL harboring <i>TCR</i> fusion. These fusions involved diverse partner genes, including <i>LINC01656</i>,<i> TBC1D10B</i>,<i> TCL1A/TCL1B</i>,<i> CDKN2A</i>,<i> CEBPB/G</i>, and <i>AHI1</i>. Patients with <i>TCR</i> fusions showed a gene expression profile enriched in hematopoietic stem cell (HSC) signatures and frequently carried other adverse genomic markers, such as <i>CDKN2A/B</i> alterations and <i>RAS</i> pathway activation. Clinically, <i>TCR-</i>rearranged B-ALL patients were associated with increased risk (<i>P</i> = 0.005) and had higher minimal residual disease (MRD) at day 19 (<i>P</i> = 0.034), and may benefit from MRD-based risk-directed therapy. Our study highlights frequent <i>TCR</i> fusions in B-ALL, suggesting a stem cell-derived leukemia with potential differentiation into both B-cell and T-cell lineages.</p>

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Frequent TCR rearrangements in pediatric B-cell lymphoblastic acute leukemia: genomic and phenotypic features

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月20日

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  • Jiajia Zheng,
  • Yiting Wang,
  • Zhiheng Li,
  • Peifang Xiao,
  • Jun Lu,
  • Hu Liu,
  • Yixin Hu,
  • Shuiyan Wu,
  • Bohan Li,
  • Li Gao,
  • Qi Ji,
  • Hailong He,
  • Yi Wang,
  • Jie Li,
  • Nan Chen,
  • Lijun Meng,
  • Yuanyuan Tian,
  • Yizhen Li,
  • Sheng Xiao,
  • Shaoyan Hu

摘要

T-cell receptor (TCR) loci undergo complex V(D)J rearrangements during T-cell maturation. However, errors in this process can cause TCR promoters and enhancers to aberrantly fuse with oncogenes, leading to their overexpression and the development of T-cell acute lymphoblastic leukemia (T-ALL). Unexpectedly, in a retrospective study of 97 pediatric B-ALL cases, all diagnosed according to WHO criteria at a single institution, we identified a subgroup of B-ALL harboring TCR fusion. These fusions involved diverse partner genes, including LINC01656, TBC1D10B, TCL1A/TCL1B, CDKN2A, CEBPB/G, and AHI1. Patients with TCR fusions showed a gene expression profile enriched in hematopoietic stem cell (HSC) signatures and frequently carried other adverse genomic markers, such as CDKN2A/B alterations and RAS pathway activation. Clinically, TCR-rearranged B-ALL patients were associated with increased risk (P = 0.005) and had higher minimal residual disease (MRD) at day 19 (P = 0.034), and may benefit from MRD-based risk-directed therapy. Our study highlights frequent TCR fusions in B-ALL, suggesting a stem cell-derived leukemia with potential differentiation into both B-cell and T-cell lineages.