Mixed chimerism of erythro- and megakaryopoiesis following allogeneic bone marrow transplantation.
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.
Thiele
J
J
Institute of Pathology, University of Cologne, Germany. j.thiele@uni-koeln.de
Wickenhauser
C
C
Kvasnicka
H M
HM
Varus
E
E
Schneider
C
C
Müller
H
H
Beelen
D W
DW
D000328:Adult; D001856:Bone Marrow Examination; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D019070:Cell Lineage; D002470:Cell Survival; D015672:Erythroid Precursor Cells / Q000737:chemistry / Q000166:cytology*; D004920:Erythropoiesis; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D006410:Hematopoiesis; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D039661:Integrin beta3 / Q000032:analysis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology* / Q000628:therapy; D008297:Male; D008533:Megakaryocytes / Q000737:chemistry / Q000166:cytology*; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology*; D012008:Recurrence; D012189:Retrospective Studies; D012730:Sex Chromosomes; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome
D039661:Integrin beta3