Affinage

DNTT

DNA nucleotidylexotransferase · UniProt P04053

Length
509 aa
Mass
58.5 kDa
Annotated
2026-06-09
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNTT (terminal deoxynucleotidyl transferase, TdT) is a template-independent DNA polymerase that generates antigen-receptor diversity by catalyzing random N-nucleotide addition to 3'-OH DNA ends at V(D)J recombination junctions; TdT-deficient mice completely lack N regions in immunoglobulin and T-cell receptor genes, while forced expression suppresses homology-directed joining and abolishes junctional homogeneity (PMID:8356451, PMID:8356452, PMID:7584135). Its expression is tightly controlled along the lymphoid trajectory: it is transiently induced on multipotent progenitors and progressively upregulated toward lymphoid commitment (PMID:35354960), and depends on IL7Rα signaling in human B-cell precursors (PMID:27658954). Transcriptionally, TdT is activated by E2A/E47 (PMID:8890174) and repressed by Ikaros dimers, which compete with an Ets activator at the promoter (PMID:11459831)—a repression relieved by CK2 phosphorylation of Ikaros and restored by PP1 (PMID:25214003)—and by a c-Myc/Max complex at the TdT initiator (PMID:7870572). Enzyme activity is further restrained by direct protein inhibitors: TdIF1 binds the Pol-beta-like region to block access to DNA ends, an inhibition relieved when TdIF1 engages double-stranded DNA (PMID:17663723), and TReP-132 binds the TdT N-terminus to suppress activity (PMID:16371131). Beyond physiological diversification, TdT primes replication slippage at NPM1 to generate AML-associated 4-bp insertions (PMID:31650162), and as a lymphoid-restricted antigen highly expressed in ALL it is both an immunotherapeutic target via HLA-A*02:01-presented peptides (PMID:34873326) and required for leukemia cell survival (PMID:30727883).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 High

    Established the core physiological function of TdT: whether it is the enzyme actually responsible for junctional N-region diversity in antigen receptors, and whether its activity shapes the choice of joining pathway.

    Evidence TdT-deficient mice with direct V(D)J junction sequencing of Ig and TCR genes

    PMID:8356451 PMID:8356452

    Open questions at the time
    • Does not define how TdT is recruited to the recombination machinery
    • Does not establish regulation of timing/level during development
  2. 1995 High

    Showed that TdT levels causally determine junctional repertoire structure, demonstrating gain-of-function suppression of canonical invariant junctions in fetal thymocytes.

    Evidence CD2-promoter TdT transgenic mice with TCR gamma-delta junction analysis

    PMID:7584135

    Open questions at the time
    • Does not address endogenous control of fetal TdT silencing
  3. 1995 Medium

    Addressed how TdT transcription is negatively controlled at its initiation site, identifying c-Myc/Max repression of the TdT initiator.

    Evidence EMSA with supershift and co-transfection reporter assays

    PMID:7870572

    Open questions at the time
    • No in vivo confirmation in developing lymphocytes
    • Mechanism of initiator repression not resolved
  4. 1996 Medium

    Identified a positive transcriptional regulator, showing TdT is a direct E2A target during early B-lineage commitment.

    Evidence E47 overexpression in fibroblasts with endogenous TdT transcription readout

    PMID:8890174

    Open questions at the time
    • Single overexpression method
    • Direct promoter occupancy not shown
  5. 1996 Medium

    Probed post-translational control of the enzyme itself, showing PKA phosphorylation can switch TdT toward endonuclease activity.

    Evidence In vitro phosphorylation of recombinant TdT and endonuclease assay on supercoiled plasmid

    PMID:8667637

    Open questions at the time
    • Single in vitro method, not validated in cells
    • Physiological relevance of endonuclease conversion unclear
  6. 2001 High

    Defined the mechanism of TdT down-regulation during thymocyte differentiation, showing Ikaros competes with an Ets activator at the promoter and couples repression to chromatin change.

    Evidence Competition binding, promoter mutagenesis in integrated reporter, chromatin accessibility, thymocyte differentiation

    PMID:11459831

    Open questions at the time
    • Identity of the Ets activator not fully resolved
    • Link between accessibility change and pericentromeric repositioning correlative
  7. 2006 Medium

    Identified a direct protein inhibitor acting through the TdT N-terminus, expanding the set of negative regulators during V(D)J recombination.

    Evidence Yeast two-hybrid, pull-down, co-IP, in vitro activity assay, co-localization in COS7 cells

    PMID:16371131

    Open questions at the time
    • In vivo relevance during recombination not established
    • Structural basis of inhibition unknown
  8. 2007 Medium

    Resolved how TdIF1 inhibits TdT and how the inhibition is relieved, mapping a DNA-sensing switch that targets TdT to AT-rich DNA.

    Evidence Domain analysis, binding assays, in vitro TdT activity assays with dsDNA primer

    PMID:17663723

    Open questions at the time
    • No structure of the TdT-TdIF1 complex
    • In vivo consequence of the dsDNA-triggered release not shown
  9. 2014 Medium

    Connected kinase/phosphatase signaling to TdT transcription, showing CK2 phosphorylation of Ikaros relieves and PP1 restores TdT repression.

    Evidence Ikaros phosphomutants, CK2/PP1 inhibitors, qChIP and qRT-PCR in thymocytes and leukemia cells

    PMID:25214003

    Open questions at the time
    • Single lab
    • Does not establish CK2-Ikaros axis as the dominant control in normal development
  10. 2016 Medium

    Established a developmental signaling input controlling TdT levels in humans, linking IL7Rα signaling to TdT expression and N-region length.

    Evidence Ig rearrangement sequencing and expression in fetal precursors and IL7Rα-deficient patient samples

    PMID:27658954

    Open questions at the time
    • Downstream effectors linking IL7Rα to TdT transcription unknown
    • Single study
  11. 2019 Medium

    Extended TdT's mutagenic activity to leukemogenesis, modeling how N-addition primes replication slippage to generate recurrent NPM1 4-bp insertions in AML.

    Evidence Large-scale analysis of 2430 NPM1 mutations with predictive statistical modeling and pediatric/adult comparison

    PMID:31650162

    Open questions at the time
    • No direct in vitro reconstitution of the slippage mechanism
    • Correlative inference of TdT activity from sequence features
  12. 2019 Medium

    Tested whether TdT is required for survival of TdT-expressing leukemia, establishing a dependency through splicing-based knockdown.

    Evidence PNA splicing modulation with apoptosis and viability readouts in Molt-4 cells

    PMID:30727883

    Open questions at the time
    • Single cell line
    • Mechanism linking TdT loss to apoptosis not defined
  13. 2021 High

    Exploited TdT as a lymphoid-restricted antigen, demonstrating engineered TCRs against TdT peptides eliminate ALL while sparing normal cells.

    Evidence TCR engineering, in vitro cytotoxicity, three B-ALL mouse models, humanized mice for normal cell sparing

    PMID:34873326

    Open questions at the time
    • Restricted to HLA-A*02:01 context
    • Long-term durability and escape not addressed
  14. 2022 High

    Mapped where TdT is first induced in hematopoiesis, identifying a multipotent progenitor subset with transient TdT and defining the lymphoid trajectory.

    Evidence TdT reporter and lineage-tracing mice with single-cell CITE-seq and differentiation assays

    PMID:35354960

    Open questions at the time
    • Transcriptional trigger for transient TdT induction in MPPs unknown
    • Functional role of TdT in MPPs beyond marking lineage not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple transcriptional, signaling, and protein-inhibitor inputs are integrated to set TdT activity precisely at the recombinase, and the structural basis of its regulation, remain unresolved.
  • No structural model of TdT bound to its protein inhibitors
  • Hierarchy among E2A activation, Ikaros/c-Myc repression, and IL7Rα control during normal development undefined
  • Direct mechanistic link between TdT and replication slippage at NPM1 not reconstituted

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0003677 DNA binding 2 GO:0016740 transferase activity 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3
Partners
IKAROSTDIF1TREP-132

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 TdT is responsible for template-independent N-region nucleotide addition at V(D)J gene segment junctions. TdT-deficient mice completely lack N regions in immunoglobulin and T cell receptor variable region genes, proving TdT is the enzyme responsible for junctional diversity. Genetic knockout (TdT-deficient mice), sequence analysis of V(D)J junctions Science High 8356451 8356452
1993 TdT expression in adult mice blocks homology-directed (P-nucleotide/microhomology) V(D)J recombination; TdT-deficient adult mice show extensive homology-directed recombination, indicating TdT's N-addition activity suppresses this alternative joining pathway. Genetic knockout (TdT-deficient mice), sequence analysis of V(D)J junctions Science High 8356451 8356452
1995 Forced TdT expression (via CD2-promoter transgene) in fetal thymus V gamma 3+ T cells markedly reduces the frequency of canonical invariant TCR gamma-delta junctions and increases non-canonical junctions with N nucleotides, demonstrating TdT activity directly inhibits junctional homogeneity in fetal thymocytes. Transgenic mouse overexpression of TdT, analysis of TCR gamma-delta junctions Immunity High 7584135
1987 TdT catalysis is strongly inhibited by Ap5A (P1,P5-bis(5'-adenosyl) pentaphosphate) through interaction at both the dNTP substrate binding domain and the DNA primer binding domain; kinetic analysis showed competitive inhibition at both sites with a Ki ~0.25 µM when both domains are available. In vitro enzyme kinetics, UV cross-linking of substrate/primer to TdT, borohydride reduction trapping with oxidized Ap5A Biochemistry High 2439117
2001 Ikaros protein dimers compete with an Ets transcription factor activator for occupancy of the TdT promoter to repress TdT transcription during CD4+CD8+ thymocyte differentiation. Mutations that selectively disrupt Ikaros binding to the integrated TdT promoter abolish down-regulation upon differentiation. Chromatin alterations accompany Ikaros-mediated TdT repression, preceding pericentromeric repositioning. Binding/competition assays, promoter mutagenesis in integrated TdT reporter, chromatin accessibility (restriction enzyme assay), differentiation of CD4+CD8+ thymocyte line Genes & development High 11459831
1996 E47 (E2A protein) activates the endogenous chromosomal TdT gene when overexpressed in non-B (fibroblast) cells, demonstrating TdT is a direct transcriptional target of E2A proteins early in B-cell lineage commitment. Stable transfection/overexpression of E47, measurement of endogenous TdT transcription The EMBO journal Medium 8890174
1995 c-Myc/Myn (Max) protein complex binds to the TdT initiator element (InrTdT) at the transcription initiation site, and c-Myc overexpression represses transcriptional activity of the TdT initiator in co-transfection assays. Gel retardation (EMSA), co-transfection/reporter assay, supershift with specific antibodies Nucleic acids research Medium 7870572
2006 TReP-132 directly binds TdT through TdT's N-terminal region and reduces TdT activity to 2.5% of maximum in vitro. TReP-132 also binds TdIF1, and all three proteins co-localize in the nucleus, suggesting TReP-132 negatively regulates TdT during V(D)J recombination. Yeast two-hybrid, pull-down assay, immunoprecipitation, in vitro TdT activity assay, co-localization by immunofluorescence in COS7 cells Genes to cells Medium 16371131
2007 TdIF1 (TdT-interacting factor 1) binds to the Pol beta-like region in TdT and blocks TdT access to DNA ends, thereby inhibiting TdT activity. In the presence of double-stranded DNA, TdIF1 binds dsDNA through AT-hook-like motif and helix-turn-helix motif, releasing TdT to concentrate near AT-rich DNA for synthesis. Functional domains in TdIF1 include TdT-binding, DNA-binding (three regions), dimerization, and a bipartite NLS overlapping the AT-hook-like motif. Bioinformatics domain analysis, binding assays (pull-down, co-IP), in vitro TdT activity assays with dsDNA primer Genes to cells Medium 17663723
2014 CK2 (Casein Kinase II) phosphorylation of Ikaros decreases Ikaros binding to the TdT promoter and reduces Ikaros-mediated transcriptional repression of TdT in thymocytes and T-cell leukemia. PP1 (Protein Phosphatase 1) activity restores Ikaros DNA-binding affinity at the TdT promoter and Ikaros-mediated TdT repression. CK2 inhibition also restores TdT repression. Ikaros phosphomimetic/phosphoresistant mutants, CK2 and PP1 inhibitors, quantitative ChIP (qChIP), qRT-PCR in primary thymocytes and leukemia cells Pediatric blood & cancer Medium 25214003
2019 TdT primes replication slippage at NPM1 to generate AML-associated 4-bp insertion mutations through N-nucleotide addition. Analysis of 2430 NPM1 mutations showed G/C-rich N-nucleotide tracts with polypurine/polypyrimidine stacking bias consistent with TdT synthesis; the TdT-mutator model predicted the relative incidence of 256 potential 4-bp insertions with significant correlation (ρ=0.484). Higher TdT activity in pediatric myeloid cells correlates with longer N-regions in pediatric vs. adult NPM1 mutations. Large-scale mutational analysis (2430 mutations), statistical modeling, comparison of pediatric vs. adult mutation spectra Blood Medium 31650162
1988 TdT mediates selective cytotoxicity of 2',3'-dideoxyadenosine (ddA) in TdT-positive cells by chain-terminating addition of ddAMP to DNA. A pre-B cell line rendered TdT-positive by retroviral TdT cDNA transduction showed 90% cell death vs. 30% in the TdT-negative parental line under ddA/coformycin treatment, directly demonstrating TdT's role in ddA cytotoxicity. Retroviral TdT cDNA transduction of TdT-negative cell line, cell viability assay with ddA/CF treatment Blood Medium 2836001
1996 Phosphorylation of recombinant TdT by protein kinase A (PKA) dramatically increases its endonuclease activity on supercoiled plasmid DNA in cell-free experiments, converting it to a linearizing endonuclease. In vitro phosphorylation of recombinant TdT by PKA, endonuclease assay on supercoiled plasmid DNA Leukemia Medium 8667637
1997 TdT has been highly conserved (>70% amino acid similarity) across vertebrate evolution (trout, chicken, Xenopus, mouse, human, cattle). Structural alignment with rat DNA polymerase beta supports the hypothesis that TdT and Pol beta evolved from a common ancestral repair polymerase. Four PKC phosphorylation sites are conserved across species, suggesting a role for PKC in TdT regulation. cDNA cloning and sequencing, Northern blot, RT-PCR, phylogenetic/structural alignment with rat Pol beta crystal structure Immunogenetics Low 9271626
2004 In the Mexican axolotl, two TdT isoforms exist: TdT1 (full-length, with all conserved catalytic motifs) and TdT2 (lacking the first helix-hairpin-helix DNA-binding motif due to 57-amino acid internal deletion). TdT and Pol mu are closely related paralogs that were already present in the common ancestor of jawed vertebrates. cDNA cloning, sequence analysis, phylogenetic analysis, RT-PCR developmental expression Immunogenetics Low 15146297
2016 In human fetal B-cell precursors, TdT expression is lower than in pediatric bone marrow precursors, correlating with fewer N-nucleotide additions in IGH gene rearrangements. IL7Rα signaling is required for TdT expression: B-cell progenitors from IL7Rα-deficient patients had reduced TdT expression and fewer N-nucleotide additions at Dh-Jh junctions. Molecular analysis of Ig gene rearrangements, quantitative expression analysis, analysis of IL7Rα-deficient patient samples Scientific reports Medium 27658954
2022 Using TdT reporter and lineage-tracing transgenic mice, transient TdT induction was detected on a newly identified multipotent progenitor (MPP) subset within MPP4 lacking self-renewal but retaining multilineage differentiation potential. Stable and progressive TdT upregulation defined the lymphoid developmental trajectory. TdT+ MPP multipotency was associated with ESAM expression, and ESAM downregulation marked progressive loss of alternative fates along all lineages. Transgenic reporter mice (TdT reporter and lineage-trace), single-cell CITE-seq, flow cytometry, differentiation assays Nature immunology High 35354960
2021 TdT-derived peptides presented on HLA-A*02:01 are recognized by specific TCRs that, when expressed in T cells, eliminate primary ALL cells of both T- and B-cell origin in vitro and in three mouse models of disseminated B-ALL, while sparing normal peripheral T and B cells and myeloid cells in vitro and in humanized mice. This is mechanistically explained by TdT being an intracellular, lymphoid-restricted antigen expressed highly in 80-94% of B- and T-ALLs but only transiently during normal lymphoid differentiation. TCR identification and engineering, in vitro cytotoxicity assays, three in vivo mouse models of B-ALL, humanized mice for normal cell sparing Nature biotechnology High 34873326
1995 Avian (chicken) TdT is expressed exclusively in the thymus (not bone marrow or bursa of Fabricius), indicating TdT plays a role in N-region addition in chicken T-cell receptor genes but not in immunoglobulin gene diversification in birds. Northern blot hybridization, RT-PCR of chicken tissues, expression of recombinant chicken TdT in bacteria with specific activity measurement Nucleic acids research Medium 7596835
2019 Downregulation of TdT expression through PNA-mediated splicing modulation (targeting intron 7 splice junctions of TdT pre-mRNA) in Molt-4 cells leads to reduced TdT protein levels, increased apoptosis, and decreased cell survival, establishing TdT as functionally required for survival of TdT-expressing leukemia cells. Antisense PNA treatment, RT-PCR (splice variant analysis), Western blot (TdT protein level), apoptosis assay, cell viability assay in Molt-4 cells Current pharmaceutical biotechnology Medium 30727883

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Lack of N regions in antigen receptor variable region genes of TdT-deficient lymphocytes. Science (New York, N.Y.) 385 8356451
1993 Mice lacking TdT: mature animals with an immature lymphocyte repertoire. Science (New York, N.Y.) 368 8356452
2000 DNA polymerase mu (Pol mu), homologous to TdT, could act as a DNA mutator in eukaryotic cells. The EMBO journal 234 10747040
2001 Down-regulation of TDT transcription in CD4(+)CD8(+) thymocytes by Ikaros proteins in direct competition with an Ets activator. Genes & development 123 11459831
1976 The distribution of terminal deoxynucleotidyl transferase (TdT) among subsets of thymocytes in the rat. Journal of immunology (Baltimore, Md. : 1950) 122 1249420
1978 Adenosine deaminase, terminal deoxynucleotidyl transferase (TdT), and cell surface markers in childhood acute leukemia. Blood 115 281253
1985 Human bone marrow cells positive for terminal deoxynucleotidyl transferase (TdT), HLA-DR, and a T cell marker may represent prothymocytes. Journal of immunology (Baltimore, Md. : 1950) 98 2413114
2002 CD56(+) TdT(+) blastic natural killer cell tumor of the skin: a primitive systemic malignancy related to myelomonocytic leukemia. Cancer 93 12015765
1996 E47 activates the Ig-heavy chain and TdT loci in non-B cells. The EMBO journal 87 8890174
2007 TdT expression in Merkel cell carcinoma: potential diagnostic pitfall with blastic hematological malignancies and expanded immunohistochemical analysis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 85 17885674
1992 The significance of CD34 and TdT determinations in patients with untreated de novo acute myeloid leukemia. Leukemia 68 1279324
1997 Characterization of rainbow trout terminal deoxynucleotidyl transferase structure and expression. TdT and RAG1 co-expression define the trout primary lymphoid tissues. Immunogenetics 65 9271626
1999 A logistic regression based extension of the TDT for continuous and categorical traits. Annals of human genetics 62 10738544
1984 TdT-positive acute leukemia with monocytoid characteristics: clinical, cytochemical, cytogenetic, and immunologic findings. Blood 61 6733275
1999 Combined sib-TDT and TDT provide evidence for linkage of the interleukin-1 gene cluster to erosive rheumatoid arthritis. Human molecular genetics 60 10441334
1991 A molecular genetic linkage map of mouse chromosome 19, including the lpr, Ly-44, and Tdt genes. Biochemical genetics 60 1684099
2012 TdT+ T-lymphoblastic populations are increased in Castleman disease, in Castleman disease in association with follicular dendritic cell tumors, and in angioimmunoblastic T-cell lymphoma. The American journal of surgical pathology 56 23060347
2005 TDT-association analysis of EKN1 and dyslexia in a Colorado twin cohort. Human genetics 54 16133186
2018 High-grade B-cell lymphomas with TdT expression: a diagnostic and classification dilemma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 52 30181564
1995 The role of short homology repeats and TdT in generation of the invariant gamma delta antigen receptor repertoire in the fetal thymus. Immunity 51 7584135
1995 Further characterisation of the in situ terminal deoxynucleotidyl transferase (TdT) assay for the flow cytometric analysis of apoptosis in drug resistant and drug sensitive leukaemic cells. Cytometry 51 7587710
2016 Target-triggered catalytic hairpin assembly and TdT-catalyzed DNA polymerization for amplified electronic detection of thrombin in human serums. Biosensors & bioelectronics 50 27592241
2001 Family-based transmission disequilibrium test (TDT) and case-control association studies reveal surfactant protein A (SP-A) susceptibility alleles for respiratory distress syndrome (RDS) and possible race differences. Clinical genetics 49 11595019
1997 MIC2, TdT, bcl-2, and CD34 expression in paraffin-embedded high-grade lymphoma/acute lymphoblastic leukemia distinguishes between distinct clinicopathologic entities. Human pathology 48 9343323
2008 Reactivity with TdT in Merkel cell carcinoma: a potential diagnostic pitfall. American journal of clinical pathology 47 18480005
1993 Terminal deoxynucleotidyl transferase (TdT) expression in acute myeloid leukemia. Leukemia 47 7688837
1996 Induction of apoptosis by cordycepin in ADA-inhibited TdT-positive leukemia cells. Leukemia 45 8667637
1983 Distinct lymphoblastic and myeloblastic populations in TdT positive acute myeloblastic leukemia: evidence by double-fluorescence staining. Leukemia research 45 6343731
1997 Linkage disequilibrium between the dopamine transporter gene (DAT1) and bipolar disorder: extending the transmission disequilibrium test (TDT) to examine genetic heterogeneity. Genetic epidemiology 43 9433566
2011 Expression of TdT in Merkel cell carcinoma and small cell lung carcinoma. American journal of clinical pathology 42 21571955
2013 Immunohistochemical expression of PAX5 and TdT by Merkel cell carcinoma and pulmonary small cell carcinoma: a potential diagnostic pitfall but useful discriminatory marker. International journal of clinical and experimental pathology 41 23329999
2013 MTHFR C677T polymorphism and risk of congenital heart defects: evidence from 29 case-control and TDT studies. PloS one 41 23536781
1995 The c-myc protein represses the lambda 5 and TdT initiators. Nucleic acids research 41 7870572
1991 Combined flow cytometric assessment of cell surface antigens and nuclear TdT for the detection of minimal residual disease in acute leukaemia. British journal of haematology 39 1998595
1984 A selective culture system for generating terminal deoxynucleotidyl transferase-positive (TdT+) lymphoid precursor cells in vitro. I. Description of the culture system. The Journal of experimental medicine 38 6210337
2016 Double- and triple-hit lymphomas can present with features suggestive of immaturity, including TdT expression, and create diagnostic challenges. Leukemia & lymphoma 37 26892631
2006 Evidence for preferential Ig gene usage and differential TdT and exonuclease activities in human naïve and memory B cells. Molecular immunology 37 17196657
2014 A TdT-mediated cascade signal amplification strategy based on dendritic DNA matrix for label-free multifunctional electrochemical biosensing. Biosensors & bioelectronics 36 25118111
1988 Translocation (6;9) may be associated with a specific TdT-positive immunological phenotype in ANLL. Leukemia 34 3347092
2022 Mutational Landscape of TdT+ Large B-cell Lymphomas Supports Their Distinction From B-lymphoblastic Neoplasms: A Multiparameter Study of a Rare and Aggressive Entity. The American journal of surgical pathology 33 34392269
2019 Molecular roulette: nucleophosmin mutations in AML are orchestrated through N-nucleotide addition by TdT. Blood 33 31650162
1997 013 (CD99) positivity in hematologic proliferations correlates with TdT positivity. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 33 9110287
2022 Dntt expression reveals developmental hierarchy and lineage specification of hematopoietic progenitors. Nature immunology 29 35354960
2021 T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes. Nature biotechnology 29 34873326
1980 A micromethod for determination of terminal deoxynucleotidyl transferase (TdT) in the diagnostic evaluation of acute leukemias. Journal of cancer research and clinical oncology 29 6935216
1988 TdT positive B-cell acute lymphoblastic leukaemia (B-ALL) without Burkitt characteristics. British journal of haematology 28 3288272
2007 VEGF C-634G polymorphism is associated with protection from isolated ventricular septal defect: case-control and TDT studies. European journal of human genetics : EJHG 27 17625508
1986 Incidence of TdT positivity in cases of leukemia and lymphoma. Acta haematologica 26 3088880
2022 Humanized V(D)J-rearranging and TdT-expressing mouse vaccine models with physiological HIV-1 broadly neutralizing antibody precursors. Proceedings of the National Academy of Sciences of the United States of America 25 36574685
2000 General equations for Pt, Ps, and the power of the TDT and the affected-sib-pair test. American journal of human genetics 25 11013135
1996 Enhancement of TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method using mung bean nuclease, a single-stranded DNA digestion enzyme. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 25 8609368
1998 In vivo incidence of apoptosis evaluated with the TdT FragEL DNA fragmentation detection kit in cartilage and bone cells of the rat tibia. Tissue & cell 24 10036787
1996 Repertoires of antigen receptors in Tdt congenitally deficient mice. International reviews of immunology 24 8884428
2006 Paucity of V-D-D-J rearrangements and VH replacement events in lupus prone and nonautoimmune TdT-/- and TdT+/+ mice. Journal of immunology (Baltimore, Md. : 1950) 23 16818769
1987 Regeneration of TdT+, pre-B, and B cells in bone marrow after allogeneic bone marrow transplantation. Transplantation 23 3296354
2019 Downregulation of TdT Expression through Splicing Modulation by Antisense Peptide Nucleic Acid (PNA). Current pharmaceutical biotechnology 22 30727883
1995 Adaptation of the TdT assay for semi-quantitative flow cytometric detection of DNA strand breaks. Cytometry 22 7587711
2017 Progression of liver fibrosis can be controlled by adequate chelation in transfusion-dependent thalassemia (TDT). Annals of hematology 21 28875336
2016 Decreased IL7Rα and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin. Scientific reports 21 27658954
2014 Protein phosphatase 1 (PP1) and Casein Kinase II (CK2) regulate Ikaros-mediated repression of TdT in thymocytes and T-cell leukemia. Pediatric blood & cancer 21 25214003
2012 TDT (-), KIT (+), CD34 (+), CD99 (+) precursor T lymphoblastic leukemia/lymphoma. International journal of clinical and experimental pathology 21 22400079
2003 N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia: TDT and case-control analyses. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 21 12707933
1988 2',3'-Dideoxyadenosine is selectively toxic for TdT-positive cells. Blood 21 2836001
2019 A "signal-on" electrochemical biosensor based on DNAzyme-driven bipedal DNA walkers and TdT-mediated cascade signal amplification strategy. Analytica chimica acta 20 31987151
1987 Multiple chromosome abnormalities in a drug resistant TdT positive B-cell leukemia. Leukemia research 20 3493393
2020 ExoIII and TdT dependent isothermal amplification (ETDA) colorimetric biosensor for ultra-sensitive detection of Hg2. Food chemistry 19 32045813
2017 In situ formed copper nanoparticles templated by TdT-mediated DNA for enhanced SPR sensor-based DNA assay. Biosensors & bioelectronics 19 28544921
1993 Differential expression of terminal transferase (TdT) in acute lymphocytic leukaemia expressing myeloid antigens and TdT positive acute myeloid leukaemia as compared to myeloid antigen negative acute lymphocytic leukaemia. British journal of haematology 19 8217792
2023 Fluorescent aptasensor based on the MNPs-CRISPR/Cas12a-TdT for the determination of nasopharyngeal carcinoma-derived exosomes. Mikrochimica acta 18 36700990
2019 Highly sensitive aflatoxin B1 sensor based on DNA-guided assembly of fluorescent probe and TdT-assisted DNA polymerization. Food chemistry 18 31126452
2002 Characterization of tdt genes for the degradation of tricyclic diterpenes by Pseudomonas diterpeniphila A19-6a. Canadian journal of microbiology 18 11888163
2002 Robust TDT-type candidate-gene association tests. Annals of human genetics 18 12174218
1990 Lack of correlation between immunoglobulin and T cell receptor gene rearrangements and TdT expression in acute myeloid leukaemia. Leukemia research 18 1689438
1987 Biochemistry of terminal deoxynucleotidyltransferase (TdT): characterization and mechanism of inhibition of TdT by P1, P5-bis(5'-adenosyl) pentaphosphate. Biochemistry 18 2439117
2021 Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features. Virchows Archiv : an international journal of pathology 17 33528622
2020 TdT Expression Is a Marker of Better Survival in Merkel Cell Carcinoma, and Expression of B-Cell Markers Is Associated With Merkel Cell Polyomavirus. American journal of clinical pathology 17 32134459
2012 Detection of CD34, TdT, CD56, CD2, CD4, and CD14 by flow cytometry is associated with NPM1 and FLT3 mutation status in cytogenetically normal acute myeloid leukemia. Clinical lymphoma, myeloma & leukemia 17 22481022
1995 T-cell specific avian TdT: characterization of the cDNA and recombinant enzyme. Nucleic acids research 17 7596835
2015 On the use of an appropriate TdT-mediated dUTP-biotin nick end labeling assay to identify apoptotic cells. Analytical biochemistry 16 25862087
2007 Identification of functional domains in TdIF1 and its inhibitory mechanism for TdT activity. Genes to cells : devoted to molecular & cellular mechanisms 16 17663723
2006 Evaluation of CD7 and terminal deoxynucleotidyl transferase (TdT) expression in CD34+ myeloblasts from patients with myelodysplastic syndrome. Leukemia research 16 16417922
2004 Early expression of two TdT isoforms in the hematopoietic system of the Mexican axolotl. Implications for the evolutionary origin of the N-nucleotide addition. Immunogenetics 16 15146297
1989 Detection of terminal deoxynucleotidyl transferase (TdT) by flow cytometry in leukemic disorders. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 16 2647840
2019 Terminal deoxynucleotidyl transferase (TdT)-catalyzed homo-nucleotides-constituted ssDNA: Inducing tunable-size nanogap for core-shell plasmonic metal nanostructure and acting as Raman reporters for detection of Escherichia coli O157:H7. Biosensors & bioelectronics 15 31203177
1998 Propidium iodide quenches the fluorescence of TdT-incorporated FITC-labeled dUTP in apoptotic cells. Cytometry 15 9845437
1995 Differential TdT expression in acute leukemia by flow cytometry: a quantitative study. Leukemia 14 7723388
1985 Antigenic phenotype of TdT-positive cells in human peripheral blood. Cellular immunology 14 3155660
2023 A Quenched Size-Expanded Nucleotide Reports Activity of the Leukemia Biomarker Terminal Deoxynucleotidyl Transferase (TdT). Angewandte Chemie (International ed. in English) 13 36880583
2018 Simultaneous Monitoring of Cell-surface Receptor and Tumor-targeted Photodynamic Therapy via TdT-initiated Poly-G-Quadruplexes. Scientific reports 13 29615769
2022 CD117, BAP1, MTAP, and TdT Is a Useful Immunohistochemical Panel to Distinguish Thymoma from Thymic Carcinoma. Cancers 12 35565429
2017 High-Grade B-Cell Neoplasm with Surface Light Chain Restriction and Tdt Coexpression Evolved in a MYC-Rearranged Diffuse Large B-Cell Lymphoma: A Dilemma in Classification. Case reports in hematology 12 28884033
2017 Terminal Deoxynucleotidyl Transferase (TdT)-negative Lymphoblastic Leukemia in Pediatric Patients: Incidence and Clinical Significance. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 12 29187045
2006 Direct binding of TReP-132 with TdT results in reduction of TdT activity. Genes to cells : devoted to molecular & cellular mechanisms 12 16371131
1997 Detection of terminal deoxynucleotidyl transferase (TdT) in nonhematopoietic small round cell tumors of children. Pediatric pathology & laboratory medicine : journal of the Society for Pediatric Pathology, affiliated with the International Paediatric Pathology Association 12 9353824
1987 Heterogeneity of TdT+, HLA-DR+ acute leukaemia: immunological, immunocytochemical and clinical evidence of lymphoid and myeloid origin. European journal of haematology 12 3036570
2020 DSN/TdT recycling digestion based cyclic amplification strategy for microRNA assay. Talanta 11 32887095
2012 Incorporating genotype uncertainties into the genotypic TDT for main effects and gene-environment interactions. Genetic epidemiology 11 22678881
1990 TdT-Positive, SmIg-Negative B Precursor Cell Leukemia with Burkitt Morphology: A Case Report. Leukemia & lymphoma 11 27456743
1986 TdT activity in acute myeloid leukemias defined by monoclonal antibodies. American journal of hematology 11 3461712
1989 TdT+/nonlymphoid antigen+ acute leukemias: immunologic and karyotypic monitoring during therapy and at relapse suggests the transformation of a bipotential stem cell. Leukemia 10 2733453

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