Establishment and characterization of a novel patient-derived TP63-rearranged anaplastic large-cell lymphoma model PTCL-S1

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Abstract
Anaplastic large-cell lymphoma (ALCL) accounts for 15% of all peripheral T-cell lymphomas globally and can be further divided into subcategories, of which patients with ALK-negative ALCL have dismal prognosis and overall survival. We established a patient-derived xenograft (PDX) and in vitro model (designated PTCL-S1) of TP63-rearranged ALK-negative ALCL from the primary tumour site of a 55-year old Chinese woman. Whole genome sequencing of the patient’s tumour identified various mutations including AKT1 and NOTCH1, as well as the TP63-TBL1XR1 gene fusion. RNA sequencing followed by Sanger sequencing confirmed the gene rearrangement in original tumour, PDX and PTCL-S1 cell line. Immunohistochemistry profiling of the PDX model and cell-line were consistent with the patient’s primary tumour sample (CD3 + /CD30 + /CD79a-). Cytotoxic agents (doxorubicin, etoposide and gemcitabine) commonly used in ALCL treatment exhibited potent anti-proliferative activity in the cell-line. In conclusion, the established PTCL-S1 cell line can be a useful tool for further investigation of the understanding of TP63-rearranged ALK-negative ALCL.
Funding Information
  • Tanoto Foundation Professorship in Medical Oncology
  • New Century Foundation Limited
  • LING Foundation
  • National Medical Research Council (TA21jun-0005, CG21APR2002)
  • National Medical Research Council (OFLCG18May-0028, OFLCG23May-0039)
  • SingHealth Duke-NUS AM/ACP-Designated Philanthropic Fund Grant Award (08/FY2023/EX/27-A65)
  • Khoo Bridge Funding Award provided by Duke-NUS Medical School and the “Estate of Tan Sri Khoo Teck Puat”. (Duke-NUS-KBrFA/2025/0090)

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