Terminal deoxynucleotidyl transferase (TdT)
Terminal deoxynucleotidyl transferase (TdT) is an unusual
deoxynucleotide polymerizing enzyme with a molecular weight of about
58 kDa found normally only in B- and T-cell
lymphoblasts/prelymphocytes. The gene is located at 10q23-q24 and
encodes a template-independent DNA polymerase that catalyzes the
addition of deoxynucleotides to the 3'-hydroxyl terminus of
oligonucleotide primers. TdT generates antigen receptor diversity by
synthesizing non-germ line elements (N-regions) at the junctions of
rearranged Ig heavy chain and T cell receptor gene segments.
Alternatively spliced transcript variants encoding long and short
isoforms of this gene have been described.
Uniform and strong expression is typical for pre-B and pre-T acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) (Fig. 2). Very weak expression is also sometimes seen in Burkitt lymphoma. All other mature (peripheral) malignant lymphomas are negative.
Acute myeloid leukemia (AML) may show expression of TdT, which is not unusual finding in AML-M0 or AML with multilineage dysplasia, but rarely can be seen in other types of AML.
Immunohistochemical detection of TdT has value in classification of malignant lymphomas and acute leukaemias, particularly for the identification of pre-B and pre-T acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL). The intensity of TdT expression is important since weak expression of TdT does not strongly support the diagnosis of ALL/LBL.
Several mAbs, e.g., SEN28 from Novocastra, and pAbs, e.g., from Dako, are available. Heat induced epitope retrieval is mandatory. An alkaline buffer is preferable.
Control tissue: Normal thymus. The cortical thymocytes should show a distinct nuclear reaction with minimal cytoplasmic staining. The medullar thymocytes should be negative.
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