Mixed chimerism of erythro- and megakaryopoiesis following allogeneic bone marrow transplantation

Acta Haematol. 2003;109(4):176-83. doi: 10.1159/000070966.

Abstract

Until now, studies on mixed chimerism (MCh) after allogeneic bone marrow transplantation (BMT) have predominantly focused on the B- and T-lymphocyte population, but not on distinct myeloid cell lineages like nucleated erythroid precursors and megakaryocytes. To evaluate the lineage-restricted MCh more explicitly in 10 patients with chronic myelogenous leukemia (CML), a quantitative analysis was performed on bone marrow biopsies following a sex-mismatched host/donor constellation. Techniques included immunophenotyping (antiglycophorin C, CD61) for the identification of erythro- and megakaryopoiesis and a simultaneously conducted genotyping with x- and y-chromosome-specific DNA probes. Normal bone marrow and specimens taken before BMT served as controls. Contrasting a total gender-dependent sex-typing in the latter samples in the early and late posttransplant period (up to 586 days), 3-9% erythroid precursors and about 16% megakaryocytes revealed a host-type origin. This significantly higher number of host megakaryocytes is explained by their polyploidy generating an increased probability to detect positive signals at a certain section level of the corresponding biopsies. A striking conversion of MCh to a recipient cell type was found in leukemic relapse with a more than 90% host-derived erythroid and megakaryocytic cell population in 4 patients approximately 643 days after BMT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Marrow Examination
  • Bone Marrow Transplantation* / adverse effects
  • Cell Lineage
  • Cell Survival
  • Erythroid Precursor Cells / chemistry
  • Erythroid Precursor Cells / cytology*
  • Erythropoiesis
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Follow-Up Studies
  • Graft Survival
  • Graft vs Host Disease / etiology
  • Hematopoiesis*
  • Humans
  • Immunophenotyping
  • In Situ Hybridization, Fluorescence
  • Integrin beta3 / analysis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
  • Male
  • Megakaryocytes / chemistry
  • Megakaryocytes / cytology*
  • Neoplastic Stem Cells / chemistry
  • Neoplastic Stem Cells / pathology*
  • Recurrence
  • Retrospective Studies
  • Sex Chromosomes
  • Tissue Donors
  • Transplantation Chimera*
  • Transplantation Conditioning
  • Transplantation, Homologous* / adverse effects
  • Treatment Outcome

Substances

  • Integrin beta3