Mixed chimerism of the resident macrophage population after allogeneic bone marrow transplantation for chronic myeloid leukemia.
BACKGROUND
Bone marrow macrophages have been recognized to play a crucial role in the functional network that constitutes the microenvironment. In chronic myelogenous leukemia (CML), neoplastic macrophages are presumably responsible for the expansion of the leukemic cell clone. So far, no information is available about a persistence of host-type macrophages after allogeneic bone marrow transplantation (BMT) implicating a lineage-specific mixed chimerism.


METHODS
Bone marrow trephine biopsies were investigated in eight male and five female patients with CML after BMT after a sex-mismatched host/donor constellation. Techniques included immunophenotyping (CD68) for identification of resident macrophages and a simultaneous genotyping with X- and Y-chromosome-specific DNA-probes (fluorescence in situ hybridization). Normal bone marrow and specimens of CML patients before BMT served as controls.


RESULTS
Contrasting an almost 100% congruence with the genotyping in the controls, a mixed chimerism of the CD68+ macrophages and the other host myeloid cells was found. Until 3 months after BMT, incidence of host-type macrophages ranged from 8% to 10%. This feature was also identifiable in the peculiar subset of pseudo-Gaucher cells (PGCs). The number of host-type macrophages failed to decline significantly during the early posttransplant period, because after almost 4 months these were still detectable. On the other hand, in patients showing an initial-to-manifest leukemic relapse, an insidious conversion of up to 50% from the donor to host-type macrophages and myeloid cells occurred.


CONCLUSIONS
The CD68+ resident bone marrow macrophage population including PGCs are involved in the lineage-specific chimerism and minimal residual disease after BMT in CML.
Wickenhauser
Claudia
C
Institute of Pathology, University of Cologne, Joseph-Stelzmannstr. 9, D-50924 Cologne, Germany.
Thiele
Juergen
J
Pérez
Fernando
F
Varus
Eva
E
Stoffel
Marc Sebastian
MS
Kvasnicka
Hans Michael
HM
Beelen
Dietrich Wilhelm
DW
Schaefer
Ullrich Wilhelm
UW
D001707:Biopsy, Needle; D001854:Bone Marrow Cells / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000628:therapy*; D008264:Macrophages / Q000473:pathology; D008297:Male; D012008:Recurrence; D012189:Retrospective Studies; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D014960:X Chromosome; D014998:Y Chromosome