Dynamics of lineage-restricted mixed chimerism following sex-mismatched allogeneic bone marrow transplantation

• J. Thiele ^[1] ; C. Wickenhauser ^[1] ; H.M. Kvasnicka ^[1] ; E. Varus ^[1] ; D.W. Beelen ^[2] ; U.W. Schaefer ^[2]
  1. [1] University of Cologne

     University of Cologne

     Kreisfreie Stadt Köln, Alemania

     
  2. [2] University of Essen
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 18, Nº. 2, 2003, págs. 557-574
• Idioma: inglés
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• Resumen

  • 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-chromosomespecific 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 molecularbiological 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.