Detection of Terminal Transferase in Leukemia

The mere presence of terminal deoxynucleotidyl transferase (TdT), a DNA polymerase, in leukemic cells provides no help in assigning these blast cells to a particular cell lineage (1 ). Differential levels of TdT gene transcription, however, result in diagnostically significant expression patterns of the enzyme with lower biochemical activity and weaker staining intensity by antibody recognition in myeloid as compared to lymphoid leukemia (2 –4 ). One major advantage of measuring TdT by flow cytometry lies in its ability to objectively reflect staining intensities, a challenging task otherwise when one evaluates antibody staining under the microscope using the standard slide technique, thereby alleviating the need for cumbersome and expensive biochemical enzyme assays. The weak fluorescence staining of TdT-expressing myeloid leukemia cells, however, until recently has caused significant technical problems in the flow cytometric TdT detection, whereas several approaches have proven successful in the flow cytometric evaluation of TdT in the intensely staining lymphoid cells (3 ). Using optimal experimental conditions, the combined analysis of nuclear TdT and surface antigens in all types of leukemia now allows for the detection of minimal residual disease at levels as low as 0.02–0.5% of abnormal cells.