title: Dynamics of lineage-restricted mixed chimerism following sex-mismatched allogeneic bone marrow transplantation.
abstract: Scant knowledge is available about the dynamics of lineage-specific mixed chimerism (Ch) following bone marrow transplantation (BMT). This review is focused on findings derived from bone marrow (BM) biopsies in patients with chronic myeloid leukemia (CML) including a sex-mismatched host/donor constellation. Appropriate techniques involved immunophenotyping by monoclonal antibodies to identify the various cell lineages, dual color fluorescence in situ hybridization (FISH) with x- and y-chromosome-specific DNA-probes and a proper detection system for a simultaneous labeling of the bcr/abl locus. A significant degree of Ch with more than 20% host CD34+ progenitors was found in the early and late (up to 200 days after BMT) posttransplant period. However, only 10% of these cells harbored the bcr/abl translocation gene. This result fits well with corresponding molecular biological findings of so-called minimal residual disease. Conversion of Ch evolved during leukemic relapse with 90% host progenitors of which 50% revealed the bcr/abl locus. A Ch of nucleated erythroid percursors (5%) and CD68+ macrophages (8%) was expressed to a significantly lower degree. The slightly increased frequency found in CD61+ megakaryocytes (16%) was probably due to the polyploid state of these cells. Similar to the CD34+ progenitor cells abrupt changes from donor to host type was associated with an insidious transformation into recurrent leukemia. The CD34+ endothelial cells showed a minor degree of Ch, because donor-derived elements ranged from 18% to 25%. Leukemic relapse was characterized by an almost complete conversion of the endothelial cells to a host type. These findings point towards a CD34+ progenitor cell origin of the (leukemic) endothelial cell layer and suggests that their dysfunction may contribute to an expansion of the neoplastic clone.
authors.affiliation: Institute of Pathology, University of Cologne, Cologne, Germany. j.thiele@uni-koeln.de
authors.forename: J
authors.initials: J
authors.lastname: Thiele
authors.forename: C
authors.initials: C
authors.lastname: Wickenhauser
authors.forename: H M
authors.initials: HM
authors.lastname: Kvasnicka
authors.forename: E
authors.initials: E
authors.lastname: Varus
authors.forename: D W
authors.initials: DW
authors.lastname: Beelen
authors.forename: U W
authors.initials: UW
authors.lastname: Schaefer
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000502:physiology*; D019070:Cell Lineage; D002678:Chimera / Q000235:genetics*; D005260:Female; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D008297:Male; D008533:Megakaryocytes / Q000502:physiology; D009364:Neoplasm Recurrence, Local; D013234:Stem Cells
chemical_list: D018952:Antigens, CD34