Terminal Deoxynucleotidyl Transferase Expression in Acute Non‐lymphoid Leukaemia: an Analysis by Immunofluorescence

Abstract

Indirect immunofluorescence for terminal transferase enzyme (TdT) was used to study the blasts of 64 patients with acute non-lymphoid leukaemia (ANLL). In 32 patients no TdT positive cells were seen. In 19 cases a small subpopulation of cells expressing TdT was detected; these constituted up to 5% of total nucleated cells, and it was not clear whether these TdT positive cells were part of the leukaemic process or represented residual normal bone marrow lymphoid cells. The remaining 13 patients had TdT positive cells accounting for 7-90% of the total. In two of these cases TdT was expressed on blasts with myeloid features, representing an aberrant expression of TdT by myeloid cells; in contrast, in three cases mixed populations of TdT positive lymphoid blasts and TdT negative myeloid blasts were observed. In the remaining cases it was not possible to determine whether the TdT positive cells had definite lymphoid or myeloid features. Cytogenetic analysis showed no evidence of the Philadelphia chromosome. Response to treatment was assessed in 11 of the 13 patients. Only one patient remitted with the initial choice of therapy (DAT); four failed to respond to initial regimes of vincristine and prednisone (V & P) while the other five patients did not respond to myelotoxic combinations (DAT). Only one patient subsequently entered complete remission on second line therapy (V & P). This group of patients with TdT+ ANLL had a particularly bad prognosis, and appeared to differ from cases of TdT positive acute undifferentiated leukaemia, which often respond to V & P therapy.

Prognostic relevance of the expression of Tdt and CD7 in 335 cases of acute myeloid leukemia

“…Tdt was significantly associated with AML-M0, M1 and CD34 thus confirming its link with immature leukemias. [7][8][9][10][11]14,15 CD7 was significantly associated with AML-M0, M1, M5, with CD34 and GP-170 45 in line with other reports which have also postulated the expansion of a pluripotent CD7…”

“…2,3 The systematic use of monoclonal antibodies (moAbs) has also allowed detection of inappropriate expression of antigens from more than one lineage, thus raising the possibility of 'lineage infidelity' or 'lineage promiscuity'. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Recognition of lymphoid antigen (LyAg)-positive AML is potentially useful for immunological detection of minimal residual disease, [20][21][22][23][24] but the prevalence and prognostic importance of LyAg expression in AML remain controversial. 5,10,11,[13][14][15]17,[25][26][27][28][29][30] In a previous study of 154 patients, we found that certain phenotypic subgroups had a worse prognosis based on the expression of CD7.…”

Variations in Morphological and Immunological Blast Cell Phenotype in a Case of Acute Leukaemia with t(4;11) Translocation

“…At pre sentation, our case exhibited both monocytoid and lymphoid morphology, but common ALL markers were expressed on 90% of the cells, and therefore on monocytoid cells. This seems to be a very rare event and to our knowledge has only been described once [8], although TdT expression has been described in non-lymphoid leukaemia [16,17]. Moreover, there was within 5 days a change in the cytologic and im munologic features, with increase of the monocytoid population, the decrease in lymphoid marker expres sion and appearence of myeloid markers.…”

“…Such lineage infi delity after relapse was described in some patients with t(4;l 1) abnormality [15]. Recently, some cases of leukaemias with coexisting lymphoid and myeloid markers on the same cells [16,17,19], or cases of acute leukaemia with two distinct lymphoid and myeloid subpopulations [4,5,7,19,6] have been published. All these findings are consistent with the hypothesis that some cases of leukaemia originate from very un differentiated cells with dual lineage capabilities.…”

Diagnostic Value of Immunological Leukemia Phenotyping

“…These immunological discrepancies might be the re sult of abnormal gene regulation in malignant cells si multaneously expressing markers from two or more cell lineages. Recently, these phenomena have increas ingly been documented [18,19]. The terms 'abnormal gene expression', 'lineage infidelity' and 'acute hybrid leukemia' have been created to describe these findings [20,21].…”