Variability of Proliferative Patterns in Acute Lymphoid Leukemia of Children

Proliferative patterns of neoplastic bone marrow in five children with untreated acute lymphoid leukemia (ALL) were studied radioautographically using a combined analysis of labeling indices and median grain counts of blast cells in mitosis and in interphase as a function of time after a single intravenous injection of ³H-thymidine. The results are interpreted as follows: (1) In at least two cases, a considerable fraction of initially labeled large blasts immediately reentered another cell cycle on completion of mitosis, as evidenced from periodicities of mitotic labeling curves. The relative number of immediately recycling cells varied from patient to patient. In all cases a certain percentage of cells following division passed through a nonproliferative phase of variable duration characterized by a small nuclear size. (2) The time parameters of the mitotic cycle of leukemic blasts differed from patient to patient, although the generation times of immediately recycling cells were close to 50 hr (47-55 hr) in at least three cases. The duration of S phase varied between approximately 20 and 40 hr. Best estimates for the duration of G₂ + ½ M ranged from 3 to 7 hr, and for mitotic time from 0.5 to 1.6 hr. (3) Leukemic bone marrow cells in all five cases of ALL had longer generation times than any nonneoplastic lymphopoietic or hemopoietic cell line of man investigated so far. (4) A continuous reentry of small leukemic blast cells into a proliferative phase and a concomitant increase in nuclear size occurred in all cases studied, thus confirming previous results obtained by other authors. Possible reutilization of label and its implications with regard to interpreting cytokinetic data in ALL are discussed.