Terminal deoxynucleotidyl transferase positive subpopulations occur in the majority of ANLL: implications for the detection of minimal disease.
A series of 60 acute nonlymphocytic leukemias (ANLL) was analyzed for the expression of terminal deoxynucleotidyl transferase (TdT). The detected TdT+ cells were studied in detail by use of double marker analyses for TdT and differentiation markers, such as myeloid markers (CD13 and CD33), B cell markers, T cell markers, and the precursor antigen CD34. In 15 (25%) of these leukemic cell samples, we found no TdT+ cells or low percentages of CD10+TdT+ cells; the latter probably represent precursor B cells. In the other 45 (75%) ANLL myeloid marker+TdT+ CD10- cells were detected, ranging from 0.1-10% (n = 24) or over 10% (n = 21) of mononuclear cells. Interestingly, a higher frequency of CD34 positivity was found on the TdT+ cells as compared to the TdT- cells, suggesting that the TdT+ cells represent an immature leukemic subpopulation. Therefore, it may be speculated that the TdT+ subpopulation contains the clonogenic ANLL cells. In two patients, in whom immunologic marker analysis was performed at initial diagnosis as well as at relapse, an expansion of the TdT+ subpopulation was documented at relapse, which may reflect a reduced differentiation capacity of the leukemic cells. Previous studies on a series of nonleukemic bone marrow and blood samples revealed that normal counterparts of myeloid marker+TdT+ cells are rare in bone marrow (less than 0.03%, if they occur at all) and that such cells are not detectable in blood. Therefore myeloid marker TdT double stainings may be useful to monitor the TdT+ leukemic subpopulation in patients with a TdT+ ANLL during and after chemotherapy. Our preliminary results on the follow-up of two such patients support this hypothesis.
Adriaansen
H J
HJ
Department of Immunology, University Hospital Dijkzigt/Erasmus University, Rotterdam, The Netherlands.
van Dongen
J J
JJ
Kappers-Klunne
M C
MC
Hählen
K
K
van 't Veer
M B
MB
Wijdenes-de Bresser
J H
JH
Holdrinet
A C
AC
Harthoorn-Lasthuizen
E J
EJ
Abels
J
J
Hooijkaas
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D001853:Bone Marrow / Q000201:enzymology / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004796:Clinical Enzyme Tests; D004253:DNA Nucleotidylexotransferase / Q000032:analysis* / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012008:Recurrence
D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D004253:DNA Nucleotidylexotransferase