CD99 (MIC2) expression in paediatric B-lineage leukaemia/lymphoma reflects maturation-associated patterns of normal B-lymphopoiesis.
We have recently shown that CD99 (MIC2) is differentially expressed during normal early B-cell development in the bone marrow (BM). Since immature B-cell precursors (BCP) are assumed to correspond to some extent to acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL) cells with respect to patterns of phenotypic differentiation, we wondered whether the particular maturation-associated expression patterns of CD99 in the normal BCP stages were conserved also in malignant cells. Therefore we compared malignant and physiological B cells from paediatric ALL/NHL and normal BM samples with respect to CD99 expression using selective gating and semi-quantitative flow cytometry. Common-ALLs (n = 45) were similar to their corresponding, very immature BCPs (stage 1) in expressing very high levels of CD99. Most pre-B ALLs (n = 16) were also CD99hi and thus differed from the patterns found in normal cytoplasmic mu-chain+ (cmu+) pre-B cells (stage 2, CD99lo). In particular, we found that those pre-B-ALL cases which were CD34+ also showed higher CD99 expression than the CD34- cases. This prompted us to investigate the levels of CD99 in those rare normal BCPs which also coexpress CD34 and cmu; these cells, which are transitory from stage 1 to stage 2, were found also CD99hi, thus precisely reflecting the patterns of CD34+ pre-B ALLs. The blasts of Burkitt-type B-cell ALL/NHL samples (n = 13) expressed considerably less CD99, similarly to the more differentiated BCP stages 2 (cmu+) and 3 (surface mu-chain+). In summary, we found that paediatric B-lineage malignancies display remarkable synchrony regarding the levels of CD99 expression compared to their putative normal counterparts.
Dworzak
M N
MN
Children's Cancer Research Institute, St Anna Kinderspital, Vienna, Austria. dworzak@ccri.univie.ac.at
Fritsch
G
G
Fleischer
C
C
Printz
D
D
Fröschl
G
G
Buchinger
P
P
Mann
G
G
Gadner
H
H
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D001854:Bone Marrow Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016922:Cellular Senescence; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D015448:Leukemia, B-Cell / Q000378:metabolism*
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules