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Absence of terminal deoxynucleotidyl transferase expression in T-ALL/LBL accumulates chromosomal abnormalities to

Hui Xiao1, Siqi Wang1, Yuejia Tang1

  • 1Department of Hematology & Oncology, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China.

International Journal of Cancer
|February 9, 2023
PubMed

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.

Keywords:
DNA damage repairT-acute lymphoblastic leukemia/lymphomachromosomal abnormalitiesdrug resistanceterminal deoxynucleotidyl transferase

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