Reentry of nondividing leukemic cells into a proliferative phase in acute childhood leukemia

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Abstract
Reentry of small leukemic blast cells into a proliferative phase was demonstrated in a 3 yr old girl with untreated acute lymphoblastic leukemia. Since the proliferating leukemic cell compartment in this disease is not self-maintaining, continual entry of cells into this compartment is necessary to prevent depletion of proliferating cells. In order to identify the source of replacement cells, the rate of change of tritiated thymidine-labeled cells in the proliferating compartment was observed by means of serial bone marrow samples under two conditions. In the first study period only 10% of small leukemic blast cells were labeled, and in the second study period 72% of this population had become lebeled. During the first period the proliferating blast cells were rapidly replaced by unlabeled cells, while during the second period the replacement cells were coming largely from a labeled cell source. The only identifiable source of cells for maintenance of the proliferating population which was virtually unlabeled during the first period and largely labeled during the second period was the population of small leukemic blast cells. The finding that the small blast cells are only temporarily nonproliferative could account for effectiveness of therapy directed primarily against a dividing cell population. Persistence of some cells with longer resting times into remission could provide a focus for subsequent relapse.