DNA nucleotidylexotransferase (TdT) (TdT)

DNA nucleotidylexotransferase (TdT) is a specialized, template-independent DNA polymerase belonging to the X family of polymerases [2, 10]. It is primarily expressed in the nucleus of immature B and T lymphocytes within the thymus and bone marrow [2, 8]. TdT's fundamental biological role is to catalyze the random addition of N-nucleotides to the V(D)J junctions during the rearrangement of antigen receptor genes, a process essential for generating the vast diversity of the adaptive immune repertoire [2, 15]. In clinical oncology, TdT serves as a critical biomarker for the diagnosis and classification of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma, as it is highly overexpressed in malignant lymphoblasts but absent in mature lymphocytes [2, 3, 10]. Due to its restricted expression and role in leukemogenesis, TdT is considered an attractive therapeutic target for the development of selective anti-cancer agents [1, 4, 17]. Experimental strategies to inhibit TdT include the use of selective non-nucleoside inhibitors, such as diketo acid derivatives, and chain-terminating nucleoside analogs like cordycepin or synthetic non-natural nucleotides [1, 5, 6, 9, 17]. While targeting TdT offers a path for selective anti-leukemic therapy, potential safety concerns include the impairment of normal lymphocyte development and the reduction of immune system diversity [2, 6, 14]. Additionally, TdT expression levels have been linked to treatment resistance in certain therapies, such as inotuzumab ozogamicin, highlighting its importance in personalized medicine [11].

Other names

Terminal deoxynucleotidyl transferaseTerminal transferaseTerminal addition enzymeDNTT

Inhibition of template-independent DNA polymerization and induction of chain termination in DNA synthesis [1, 4, 5, 9].