IMBALANCE IN NUCLEOTIDE POOLS OF MYELOID LEUKEMIA CELLS AND HL-60 CELLS: CORRELATION WITH CELL CYCLE PHASE,CELL PROLIFERATION AND DIFFERENTIATION: 53

摘要

Peripheral blood myelocytes from AML or CML patients as well as HL-60 cell-line cells show an imbalance in the nucleotide pool compared with normal peripheral neutrophils. This imbalance includes a decreased ratio of purine:pyrimidine nucleotides, and an increase in the relative concentrations together with an altered composition of the UDP-sugars. First, we studied the relation between this imbalance and the cell cycle. HL-60 cells were separated into fractions enriched in Gl, s, or G2+M phase by elutriation centrifugation. The amount of nucleotides per cell differed during the cell-cycle (G2+M>S>G1), but the imbalance was found in all phases. Next, we studied the relation between the imbalance and the proliferation and/or immaturity of the cells. HL-60 cells were induced to myeloid differentation with DMSO: after 3 days of incubation proliferation stopped and after 6 days 70-90% of the cells reduced NBT upon stimulation with PMA. The nucleotide content and the imbalance diminished during differentiation, but this was also observed in non-induced non-proliferation HL-60 cells (negative NBT test). However, only DMSO-induced HL-60 cells showed a decreased UDP-sugar content,with relatively more UDP-glucose (as do normal peripheral neutrophils). We conclude, that the imbalance in the nucleotide pool of HL-60 and myeloid leukemia cells is largely related to proliferation, without differences between cell phases, whereas the changes in the UDP-sugars are associated with the immature and/or transformed character of the cells.