Frequent TCR rearrangements in pediatric B-cell lymphoblastic acute leukemia: genomic and phenotypic features
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.
Authors
- Qi Ji (ORCID: https://orcid.org/0009-0002-6514-8586)
- Hailong He
- Yuanyuan Tian (ORCID: https://orcid.org/0000-0003-3111-1961)
- Yi Wang (ORCID: https://orcid.org/0000-0001-5658-9000)
- Shaoyan Hu (ORCID: https://orcid.org/0000-0002-3386-6957)
- Shuiyan Wu (ORCID: https://orcid.org/0000-0002-8963-5082)
- Jiajia Zheng (ORCID: https://orcid.org/0000-0002-3431-8151)
- Hu Liu (ORCID: https://orcid.org/0000-0001-6774-6868)
- Nan Chen (ORCID: https://orcid.org/0000-0001-8536-6631)
- Bohan Li (ORCID: https://orcid.org/0000-0003-2952-146X)
- Jie Li (ORCID: https://orcid.org/0000-0002-1558-8623)
- Lijun Meng
- Yizhen Li (ORCID: https://orcid.org/0000-0001-8941-6691)
- Li Gao (ORCID: https://orcid.org/0000-0001-5743-8474)
- Sheng Xiao
- Zhiheng Li (ORCID: https://orcid.org/0000-0002-6968-6982)
- Yixin Hu (ORCID: https://orcid.org/0000-0002-4686-3747)
- Yi‐Ting Wang (ORCID: https://orcid.org/0000-0003-2008-4435)
- Jun Lü (ORCID: https://orcid.org/0009-0000-6292-2252)
- Peifang Xiao (ORCID: https://orcid.org/0000-0002-8237-7930)
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Soochow University (CN)
- Suzhou Research Institute (CN)
- Children's Hospital of Suzhou University (CN)
Publication Details
- Journal
- Annals of Hematology
- Published
- 2025-10-20
- DOI
- https://doi.org/10.1007/s00277-025-06687-2
- Primary Topic
- Acute Lymphoblastic Leukemia research
- Type
- article
- Field-Weighted Citation Impact
- 0.00