Analysis of cell cycle characteristics and course of the disease in ANLL

Abstract

The cell cycle characteristics of a newly diagnosed patient with acute nonlymphocytic leukemia (ANLL) were studied by using intravenous bromodeoxyuridine (BrdU) and our previously described “double‐label” technique. The percentage of S‐phase cells in the bone marrow (BM) biopsy were 25 % compared to 7 % from the simultaneously obtained BM aspirate. The duration of S‐phase (T_s) was determined to be 4 hr and the total cell cycle time (T_c) was 16 hr. We demonstrated that the actual clinical course of this patient's illness corresponded well with the course predicted on the basis of these cell cycle measurements. Although he achieved aplasia in response to two successive courses of induction chemotherapy, leukemic cells repopulated the marrow, producing a rapidly rising PB white blood cell (WBC) count with a T1/2 of approximately 20 hr each time. It is likely that the resistance of this patient's leukemia to therapy was a result of the rapid proliferative rate of his leukemic cells and not due to the inability of chemotherapeutic agents to kill a large number of cells. Since the measurements can be completed within 48 hr, measuring T_s and T_c will provide a better understanding of the biological differences that exist between patients with ANLL.