Multiparameter phenotype mapping of normal and post-chemotherapy B lymphopoiesis in pediatric bone marrow.
We studied the differentiation profiles of B cell precursors (BCP) in normal and post-chemotherapy pediatric bone marrow (BM) using multiparameter flow cytometry. The goal of our study was to draw a comprehensive phenotypic map of the three major maturational BCP stages in BM. By correlating lineage-associated markers, CD45RA, and several adhesion molecules, the stage-specific patterns were found to differ in certain details from previously published concepts. Among the earliest BCP, a subset of CD34+ CD10(lo) precursors was repeatedly observed in addition to the well characterized CD34+ CD10(hi) CD19+ majority of cells. Only two-thirds of these CD34+ CD10(lo) cells expressed CD19. However, uniformity of phenotypic features, absence of T lineage markers, and the regeneration kinetics after chemotherapy suggest the B lineage affiliation of the CD34+ CD10(lo) precursors in general. In the more mature BCP, expression of CD10, CD20, cytoplasmic and surface mu chains (c mu and s mu) was observed to overlap more than previously recognized. We found that CD20 and c mu appear early during B cell ontogeny (already on CD34+ BCP), and that CD10 is lost late, following the onset of s mu expression. Differences between normal and post-chemotherapy BM specimens regarding the phenotypic appearance of BCP were exclusively due to differences in the subset composition, as post-chemotherapy samples showed a preponderance of immature stages. Our observations may build a framework for comparing leukemic cells with their normal counterparts to define possible leukemia-associated aberrations useful for residual disease studies.
Dworzak
M N
MN
Children's Cancer Research Institute, St Anna Kinderspital, Vienna, Austria.
Fritsch
G
G
Fleischer
C
C
Printz
D
D
Fröschl
G
G
Buchinger
P
P
Mann
G
G
Gadner
H
H
D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology*; D001854:Bone Marrow Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000378:metabolism; D016130:Immunophenotyping; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell