Cell cycle kinetics in childhood acute leukemia studied with in vitro bromodeoxyuridine labeling, Ki67-reactivity, and flow cytometry.

Cell cycle kinetics of childhood acute leukemia were determined by the in vitro labeling of marrow blast cells with bromodeoxyuridine (BrdUrd) and subsequent flow cytometry of BrdUrd/DNA and Ki67/DNA in 18 patients with acute lymphocytic leukemia (ALL) and eight patients with acute nonlymphocytic leukemia (ANLL). The BrdUrd-labeling index (BrdUrd-LI) and the duration of S phase (Ts) were calculated from the slope of the regression line obtained by plotting the serial labeling indices against the labeling time. The Ts and potential doubling time (DTpot) of marrow leukemia cells varied from 6.1 to 34.3 h (median 14.3 h) and 1.1 to 20.7 days (median, 7.3 days), respectively. The duration of the total cell cycle time (Tc) which was determined by the Ki-67-derived growth fraction (Ki-67-GF) varied from 14.0 to 112.5 h (median 43.2 h). BrdUrd-LI, DTpot, Ki-67-GF and Tc were significantly correlated with the subtypes (early B-ALL, T/B- ALL and ANLL) of the disease. The median values of LI and GF were much lower in ANLL than in ALL. However, the low proliferative activity of ANLL was not accompanied by a prolonged duration of the total cell cycle time. The longest median duration of Tc was noted in early B-ALL (75.2 h) and the median Tc in ANLL (36.7 h) was close to that in T/B-ALL (34 h). Ts appeared to be rather independent of subtypes of the disease. These results show that there are distinct in vitro growth characteristics in relation to the subtypes of childhood acute leukemia.