Mixed chimerism of bone marrow CD34+ progenitor cells (genotyping, bcr/abl analysis) after allogeneic transplantation for chronic myelogenous leukemia.
BACKGROUND
Although CD34 progenitors play a crucial role during bone marrow transplantation (BMT), there is only scant knowledge concerning their lineage-restricted mixed chimerism (MCh).


METHODS
An immunohistochemical and fluorescence in situ hybridization study was performed on bone marrow biopsies derived from 11 patients with chronic myelogenous leukemia after sex-mismatched BMT to quantify the CD34 cell population and their expression. After proper identification by a lineage-specific monoclonal antibody, X chromosome- and Y chromosome-specific probes were used for sex typing and for labeling of the locus commercially available detection systems were applied.


RESULTS
After successful engraftment, 241 progenitor cells were identified at days 9 to 586 of the posttransplant period. Overall incidence of MCh was 24% with a tendency to decline after day 100 to 15%. The gene was detectable in only 10% of these precursors and decreased to less than 4% after more than 6 months. Approximately 0.5 to 5.5 years after BMT in six patients, a manifest leukemic relapse occurred, which was accompanied by a conversion of donor-to-host-type progenitors. This phenomenon involved up to 94% of the 303 evaluable CD34 cells and also included a retrieval of the translocation gene in approximately 50% of this population.


CONCLUSIONS
The lineage-restricted MCh of progenitors after BMT is in keeping with the assumption that leukemic (bcr/abl ) precursors represent only a fraction of the total host-derived (chimeric) CD34 cells. These residual clonally transformed progenitors survive myeloablative treatment and thus may be the source for a later relapse.
Thiele
Juergen
J
Institute of Pathology, University of Cologne, Cologne, Germany. j.thiele@uni-koeln.de.
Wickenhauser
Claudia
C
Kvasnicka
Hans Michael
HM
Varus
Eva
E
Kleppe
Stephanie
S
Beelen
Dietrich Wilhelm
DW
Schaefer
Ullrich Wilhelm
UW
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis*; D016026:Bone Marrow Transplantation; D005260:Female; D015870:Gene Expression; D016313:Genes, abl / Q000235:genetics*; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000601:surgery*; D008297:Male; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
D018952:Antigens, CD34