Leukemia-associated marker combinations in acute leukemia suitable for detection of minimal residual disease.
In the absence of truly leukemia-specific antigen, antigen combinations were identified in leukemia cells that are absent or extremely rare among normal hemopoietic cells. Some of the studied combinations related to the simultaneous surface and cytoplasmic marker expression, others, expressed mainly on cell surface membrane, represented atypical or aberrant combinations. Comparing membrane (m) and cytoplasmic (c) antigen expression (followed in 23 acute leukemia cases), we observed that CD3 could be detected in cytoplasm in the majority of T-ALL cells, while was absent on cell surface membrane where simultaneous expression of more immature T cell markers, such as CD7 and CD5, could be detected. Combination of mCD7/cCD3 could be regarded as a suitable marker of individual T-ALL cells. In cases of B-precursors of acute leukemia cells, leukemia-related combination of mCD19/cCD22 was found, which could characterize a single leukemia cell. The cells in one of 11 AML followed cases were positive for CD13 in cytoplasm, but not on cell surface membrane, where CD33 and other myeloid antigens were expressed. The cells in another two AML cases were positive for CD11 in cytoplasm but not on cell surface membrane, where CD13 or CD33 were expressed. Again, marker combinations of mCD33/cCD13 and mCD13 or mCD33/cCD11, respectively, represent a leukemia-related feature, suitable for tracing single leukemia cells in double immunofluorescence. Acute leukemia defined by the coexpression on most blast cells of antigens classically attributed to different lineages (referred as atypical/aberrant marker combinations) remains a rare event. We isolated a series of 27 (12%) such cases of 225 acute leukemia patients whose cells were immunophenotyped at diagnosis. Myeloid markers were present in T-ALL of two cases, T and B markers were coexpressed in 13 cases, markers of B and myeloid lineage were associated in one case, and T cell and myeloid antigens were found in 10 AML cases; in one AML case (M3 according to FAB classification) an aberrant nuclear coexpression of TdT was observed. In one case of the last group an interesting antigen combination of CD4/CD34 present in AML with monocytic differentiation was observed. When 5 patients with leukemia-associated (aberrant) markers were again analyzed at relapse, the relevant antigen combinations were retained in all of them. In summary, 44 of 50 cases (88%) from our acute leukemia series studied for leukemia-associated antigen combination, both with surface membrane and cytoplasmic marker combinations and those with aberrant markers coexpression allow the detection of minimal residual disease.
Babusíková
O
O
Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia.
Mesárosová
A
A
Koníková
M
M
Kusenda
J
J
Glasová
M
M
Klobusická
M
M
D000328:Adult; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis* / Q000097:blood; D000954:Antigens, Surface / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D002051:Burkitt Lymphoma / Q000097:blood / Q000175:diagnosis*; D002648:Child; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000175:diagnosis; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000175:diagnosis*; D012008:Recurrence
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D006684:HLA-DR Antigens