T-急性淋巴细胞白血病/淋巴瘤（T-ALL/LBL）是一种未成熟淋巴母细胞的恶性肿瘤。末端脱氧核苷酸转移酶（TDT）是一种独立于模板的DNA聚合酶，对免疫球蛋白基因的多样性生成起至关重要的作用。TDT-的T-ALL/LBL患者有更差的预后。然而，TDT-如何促进T-ALL/LBL的疾病进展尚不清楚。在这里，我们分析了上海儿童医学中心（SCMC）的T-ALL/LBL患者的预后，并证实TDT-患者复发率和缓解失败率更高，预后更差。细胞实验证明TDT参与DNA损伤修复。TDT敲除延迟DNA修复，阻滞细胞周期并降低凋亡，诱导染色体异常累积和对异常核型的耐受性。我们的研究表明，TDT- T-ALL/LBL的不良预后可能是由染色体异常引起的药物耐受性（VP16和MTX）。我们的发现揭示了TDT在T-ALL/LBL中的新功能和机制，并支持造血干细胞移植（HSCT）可能是这些患者的更好选择。© 2023 UICC。

T-acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a malignant neoplasm of immature lymphoblasts. Terminal deoxynucleotidyl transferase (TDT) is a template-independent DNA polymerase that plays an essential role in generating diversity for immunoglobulin genes. T-ALL/LBL patients with TDT- have a worse prognosis. However, how TDT- promotes the disease progression of T-ALL/LBL remains unknown. Here we analyzed the prognosis of T-ALL/LBL patients in Shanghai Children's Medical Center (SCMC) and confirmed that TDT- patients had a higher rate of recurrence and remission failure and worse outcomes. Cellular experiments demonstrated that TDT was involved in DNA damage repair. TDT knockout delayed DNA repair, arrested the cell cycle and decreased apoptosis to induce the accumulation of chromosomal abnormalities and tolerance to abnormal karyotypes. Our study demonstrated that the poor outcomes in TDT- T-ALL/LBL might be due to the drug resistance (VP16 and MTX) induced by chromosomal abnormalities. Our findings revealed novel functions and mechanisms of TDT in T-ALL/LBL and supported that hematopoietic stem cell transplantation (HSCT) might be a better choice for these patients.© 2023 UICC.