Multiparameter phenotype mapping of normal and post-chemotherapy B lymphopoiesis in pediatric bone marrow

Leukemia. 1997 Aug;11(8):1266-73. doi: 10.1038/sj.leu.2400732.

Abstract

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.

MeSH terms

  • Adolescent
  • Antigens, CD / analysis
  • Antigens, Differentiation, B-Lymphocyte / analysis
  • Antineoplastic Agents / pharmacology
  • B-Lymphocytes / cytology*
  • Bone Marrow Cells*
  • Cell Adhesion Molecules / metabolism
  • Cell Differentiation
  • Child
  • Child, Preschool
  • Flow Cytometry
  • Hematopoiesis* / drug effects
  • Humans
  • Immunoglobulin mu-Chains / metabolism
  • Immunophenotyping
  • Leukemia / drug therapy
  • Leukemia / pathology
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / pathology
  • Receptors, Antigen, B-Cell / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • Antineoplastic Agents
  • Cell Adhesion Molecules
  • Immunoglobulin mu-Chains
  • Receptors, Antigen, B-Cell