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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Jörn Erlecke; Isabell Hartmann; Martin Hoffmann; Torsten Kroll; Heike Starke; Anita Heller; Alexander Gloria; Herbert G Sayer; Tilman Johannes; Uwe Claussen; Thomas Liehr; Ivan F Loncarevic Journal: Mol Cytogenet Date: 2009-05-29 Impact factor: 2.009