title: Haemopoietic defect and decreased expansion potential of bone marrow autografts from patients with acute myeloid leukaemia in first remission.
abstract: Autologous bone marrow (BM) transplantation for acute myeloid leukaemia (AML) in complete remission (CR) is frequently followed by a slow haemopoietic recovery. We assessed the haemopoietic capacity of purified BM stem cell (CD34+ DR-) and progenitor cell (CD34+ DR+) populations from patients with AML in CR, and compared these data with those of normal BM. The feasibility of ex vivo expansion in stroma-conditioned medium supplemented with cytokines was also investigated. The number of CFU-GM produced by initial patient CD34+ DR- cells was decreased compared to normal, whereas these values were similar to normal for CD34+ DR+ cells. BFU-E, HPP-CFC and LTC-IC were reduced for both patient CD34+ DR- and CD34+ DR+ subpopulations. In contrast to normal, the patient CD34+ DR- fraction was not enriched in LTC-IC. CFU-GM expansion from patient CD34+ DR- cells was poor and decreased after 14 d of culture. No HPP-CFC expansion could be observed for patient cells. LTC-IC were below the level of detection after 14-21 d of expansion culture of CD34+ DR- patient cells, whereas they were variably maintained or expanded for normal cells. After expansion culture, cytogenetic and/or FISH analyses did not reveal the anomalies present at diagnosis, regardless of the cell subpopulation analysed. In conclusion, BM cells of patients with AML in CR show a profound defect at the level of a stem cell enriched population. No meaningful ex vivo expansion could be obtained in culture conditions allowing for a significant expansion from a normal stem cell population.
authors.affiliation: Haematology Department, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Straetmans
authors.forename: P
authors.initials: P
authors.lastname: Herman
authors.forename: D R
authors.initials: DR
authors.lastname: Van Bockstaele
authors.forename: L
authors.initials: L
authors.lastname: Michaux
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: A
authors.initials: A
authors.lastname: Ferrant
mesh_terms: D000208:Acute Disease; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured
chemical_list: D018952:Antigens, CD34