Differences in cell cycle characteristics among patients with acute nonlymphocytic leukemia

Abstract

The proliferative characteristics of myeloid leukemias were defined in vivo after intravenous infusions of bromodeoxyuridine (BrdU) in 40 patients. The percentage of S-phase cells obtained from the biopsies (mean, 20%) were significantly higher (P = .00003) than those determined from the bone marrow (BM) aspirates (mean, 9%). The post-BrdU infusion BM aspirates from 40 patients were incubated with tritiated thymidine in vitro. These double-labeled slides were utilized to determine the duration of S-phase (T(s)) in myeloblasts and their total cell cycle time (T(c)). The T(s) varied from four to 49 hours (mean, 19 hours; median, 17 hours). Similarly, there were wide variations in T(c) of individual patients ranging from 16 to 292 hours (mean, 93 hours; median, 76 hours). There was no relationship between T(c) and the percentage of S-phase cells, but there was a good correlation between T(c) and T(s) (r = .8). Patients with relapsed acute nonlymphocytic leukemia (ANLL) appeared to have a longer T(s) and T(c) than those studied at initial diagnosis. A subgroup of patients at either extreme of T(c) were identified who demonstrated clinically documented resistance in response to multiple courses of chemotherapy. We conclude that T(s) and T(c) provide additional biologic information that may be valuable in understanding the variations observed in the natural history of ANLL.