Clinical signficance of long-term cultures of myeloid blood cells

Abstract

The long-term maintenance of primitive hemopoietic precursor populations in cultures of human marrow was first described in 1981. This system, which was developed following previous work with murine marrow, appears to establish conditions that reproducibly allow the continuous turnover of a number of primitive progenitor cells, detected by their capacity upon transfer into semisolid assay cultures to generate limited numbers and types of mature blood cells. If not transferred, only those hemopoietic cells that are committed to the granulopoietic pathway are able to undergo terminal maturation. The demonstrated localization of the most primitive hemopoietic cells within the adherent fraction, primarily composed of nonhemopoietic mesenchymal elements expressing markers of fibroblasts, adipocytes, endothelial cells, and smooth-muscle cells has provided indirect evidence that interactions between these cells may be key to the survival and functional integrity of normal stem cells in this system. Such a concept has received additional support from recent studies on the cell cycle control of primitive hemopoietic cells located in and dependent on this adherent network of nonhemopoietic elements. Applications of this culture system to neoplastic populations of hemopoietic cells has revealed a number of intriguing differences in their behavior. Under conditions where maintenance of neoplastic hemopoiesis can be achieved, the most primitive progenitor classes remain continuously in cycle as they do in vivo. Thus the same inability to respond to signals that induce a noncycling state in their normal counterparts appears to be reproduced in the long-term culture system. For some populations, e.g., most CML marrows and many AML marrows, neoplastic hemopoiesis fails to become established. Although the reasons for this are not yet clear, this behavior is of interest, not only because it offers a sensitive method for detecting residual normal cells, but also as a practical approach to purging marrows of leukemic cells for autologous marrow transplantation.