SISTER CHROMATID DIFFERENTIATION AND CELL-CYCLE-SPECIFIC PATTERNS IN CHRONIC MYELOCYTIC-LEUKEMIA AND NORMAL BONE-MARROW

After in vitro incubation with bromodeoxyuridine (BrdUrd)-containing medium, metaphases of Philadephia (Ph1)-chromosome positive cells in the blood and/or bone marrow of 8 untreated patients with chronic myelocytic leukemia (CML) were analyzed by means of sister chromatid differentiation (SCD) and compared to 10 normal bone marrows. The majority of proliferating Ph1-positive cells (range: 46-86%) were unable to complete more than one cell cycle during the culture period of 50 h (M1 metaphases). Ph1-positive M2 metaphases which had completed 2 cell cycles were found in the range of 18-54% and almost no M3 metaphases were detected after passage through three cell cycles (0-1%). The corresponding findings in proliferating normal bone-marrow cells were: M1 (13-68%), M2 (30-79%) and M3 (0-18%). These data support the notion that there is a prolonged cell cycle time in CML which can be measured by SCD, demonstrating a proportional shift from M3/M2 to M1 metaphases. SCD is suggested for kinetic studies on human malignant cell clones characterized by marker chromosomes.