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

建立和表征一种新型患者来源的TP63重排间变性大细胞淋巴瘤模型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.

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