The Department of Pathology and Laboratory Medicine

Volume 1, Issue 2
August/September 1995

Hematopoietic Cell Markers:
Terminal Deoxynucleotidyl Transferase (TdT)

Authors:
Anwar Mikhael, M.D., Ph.D., Hematopathology Fellow
Harold R. Schumacher, M.D., Professor of Pathology

Clinical Utility of TdT Analysis
Terminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase which catalyzes the polymerization of deoxyribonucleotides to the 3'hydroxy end of the growing DNA molecule in the absence of a DNA template.(1) It is of interest in clinical medicine and hematopathology because high levels of activity are seen in white blood cells of patients with certain leukemias.

TdT is normally detected in cortical thymocytes, pre-B cells and rare hematopoietic elements in the bone marrow. The level of both recombinase enzymes and TdT decrease dramatically in mature lymphocytes by a mechanism which is not well understood. Increased expression of TdT occurs in:

  • Acute lymphoblastic leukemia (ALL). With the exception of Burkitt's and B cell FAB L-3 all ALL's express TdT.
  • Lymphoblastic crisis of chronic myelogenous leukemia (CML-BC-ALL)
  • Lymphoblastic lymphoma.
  • Some non-lymphocytic leukemias express TdT positivity, but there is less intensity and greater variability.

Laboratory Evaluation
The first method for detecting TdT was an impractical bioassay which required large numbers of fresh cells obtained from cell extracts.

Indirect immunofluorescence and immunoperoxidase methods developed in the 1970's, allowed for the more routine detection of TdT in a number of types of clinical specimens.(2)

TABLE 1.
Summary of the findings for TdT and myeloperoxidase (MP) in various hematological malignancies
Diagnosis TdTMP
Leukemia
FAB L-1 + -
FAB L-2 + -
FAB L-3 - -
FAB M-1 -/+ +
FAB M-2 -/+ +
FAB M-3 -/+ +
FAB M-4 -/+ +
FAB M-5 -/+ +/-
FAB M-6 -/+ +/-
FAB M-7 - -
CML-BC-ALL +-
AML - +
Lymphoma +-
Lymphoblastic +-
NHL - -
Hodgkin's Disease - -
Abbreviations used:
FAB - French American British
NHL - Non-Hodgkin's Lymphoma

Recently a flow cytometric technique has been developed for evaluation of TdT which has a number of advantages over the microscopic techniques used pre-viously; the most important being simultaneous determination of additional immunophenotypic markers. Also, methods capable of evaluating TdT in paraffin sections have been utilized with great advantage on archival material.(3)

Summary

  • TdT is an important diagnostic hematopoietic marker.
  • TdT is a unique DNA polymerase expressed in 95% of all ALL's, CML-BC-ALL, lymphoblastic lymphoma, and some non-lymphocytic leukemias.
  • TdT can be measured by bioassay, indirect immunofluorescence, immunoperoxidase, immunoalkaline phosphatase, flow cytometry and in paraffin sections.

References
  1. Schumacher HR: Cytochemistry and terminal deoxynucleotidyl transferase in Acute Leukemia: Approach to Diagnosis. Igaku-Shoin, New York - Tokyo, 1990, pp 33-50.
  2. Lanham GR, Melvin SL, Stass SA et al: Immunoperoxidase determination of TdT in acute leukemia using PAP and ABC methods. Experience in 102 cases. Am J Clin Path 83: 366-370, 1986.
  3. Orazi A, Cotton J, Cottoretti G et al: Terminal deoxynucleotidyl transferase staining in acute leukemia and normal bone marrow in routinely processed paraffin sections. Am J Clin Path 102: 640-645, 1994.


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