Sister chromatid differentiation and cell-cycle-specific patterns in chronic myelocytic leukemia and normal bone...

After in vitro incubation with bromodeoxyuridine (BrdUrd)-containing medium, metaphases of Philadelphia (Ph1)-chromosome positive cells in the blood and/or bone marrow of eight untreated patients with chronic myelocytic leukemia (CML) were analysed 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 (MI metaphases). Ph1-positive M2 metaphases which had completed two 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: MI (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 MI metaphases. SCD is suggested for kinetic studies on human malignant cell clones characterized by marker chromosomes.