British Journal of Haematology vol:101 issue:3 pages:571-81
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.