Functional differences between CD38^-and DR^-subfractions of CD34⁺bone marrow cells

Several studies have previously demonstrated enrichment in primitive progenitor cells in subfractions of CD34+bone marrow (BM) cells not expressing CD38 or HLA-DR (DR) antigens. However, no studies have directly compared these two cell populations with regard to their content of primitive and more committed progenitor cells. Flow cytometric analysis of immunomagnetic isolated CD34+cells demonstrated little overlap between CD34+CD38-and CD34+DR-progenitor subpopulations in that only 12% to 14% of total CD34+DR-and CD34+CD38-cells were double negative (CD34+CD38-DR-). Although the number of committed myeloid progenitor cells (colony- forming units granulocyte-macrophage) was reduced in both subpopulations, only CD34+CD38-cells were significantly depleted in committed erythroid progenitor cells (burst-forming units-erythroid). In single-cell assay, CD34+CD38-cells showed consistently poorer response to single as opposed to multiple hematopoietic growth factors as compared with unfractionated CD34+cells, indicating that the CD34+CD38-subset is relatively enriched in primitive hematopoietic progenitor cells. Furthermore, CD34+CD38-and CD34+DR-cells, respectively, formed 3.2-fold and 1.6-fold more high proliferative potential colony-forming cell (HPP-CFC) colonies than did unfractionated CD34+cells. Finally, CD34+CD38-DR-cells were depleted in HPP-CFCs as compared with CD34+CD38+DR+cells. The results of the present study suggest that both the CD38-and DR-subfractions of CD34+bone marrow cells are enriched in primitive hematopoietic progenitor cells, with the CD34+CD38-subpopulation being more highly enriched than CD34+DR-cells.