Low proportion of G0-phase cells during induction chemotherapy correlates with subsequent remission in acute myeloid...

Kinetic resistance is assumed to be one of the main mechanisms of drug resistance in acute myeloid leukemia (AML), but the relationship between cell cycle status at diagnosis and achievement of complete remission (CR) is controversial. Based on the possibility that the cell cycle data after starting induction chemotherapy are more important than the pretreatment data, we used 3-color flow cytometry to examine the cell cycle (G0, G1, S, and G2/M phases) of AML cells on days 0, 5, and 9 of the first induction chemotherapy in 20 patients. Cell cycle data at these 3 time points were compared in the patients who achieved CR (CR cases) and in the patients who had persistent leukemia (non-CR cases) after the induction chemotherapy. In the CR cases, there was a tendency for the percentages of G0-phase AML cells on days 5 and 9 to be smaller than that on day 0, while the opposite tendency was observed in the non-CR cases. When cell cycle data were compared between the CR and non-CR cases, the percentage of G0-phase AML cells on day 9 differed significantly (CR cases 6.9% +/- 10.9%, non-CR cases 50.1% +/- 38.4%; P = .0024). This significance remained when the patients' AML subtype was taken into consideration. None of the other cell cycle data at each time point or the hematologic parameters, which may be related to CR achievement, showed differences between the CR and non-CR cases. We emphasize the importance of cell cycle analysis after initiating therapy and suggest that such analysis can identify refractory AML subjects. The identified subjects may be candidates for clinical trials of cell cycle modulators.