Capability of Various Cytokines to Induce Quiescent Myeloid Leukemia Cells to the Proliferative Stage

Abstract

In order to investigate the capability of cytokines to induce myeloid leukemia cells from G₀ phase to the proliferative stage, blasts from 9 patients with AML and 1 patient with CML-MC were cultured with various cytokines (IL-3, GM-CSF, IL-3 -I- GM-CSF, G-CSF) for 48 hours or 96 hours in a serum-free culture system. Cells were analyzed by two-color flow cytometry, using PI and the monoclonal antibody Ki-67. The percentage of cells in G₀ phase was reduced significantly when the cells were cultured with IL-3 (p < 0.01), GM-CSF (p < 0.01), and IL-3 + GM-CSF (p < 0.01) for 48 hours, as compared with the percentage of cells in G₀ phase before culture. Moreover, the percentage of cells in S phase increased significantly when the cells were cultured with IL-3 (p < 0.01), GM-CSF (p < 0.02), and IL-3 + GM-CSF (p < 0.01) for 48 hours, as compared with the percentage of cells in S phase before culture. It is well known that many drugs which are widely used in the treatment of acute leukemia are cytotoxic mainly to proliferating cells, so that if quiescent G₀ phase cells can be induced to the proliferative stage, the treatment of acute leukemia would become more effective. The present findings showed that a considerable variation was observed among individual patients in the induction of the G₀ component to the proliferative stage. It may be possible to choose the patients to whom pre-administration with cytokines before chemotherapy may be effective, and select the cytokine likely to be the most effective for this purpose using this kind of in vitro study. These types of cytokine therapy might be able to improve the results of therapy in leukemia by decreasing the relapse rate.

Key Words:

• Myeloid leukemia cell
• IL-3
• GM-CSF
• G-CSF
• Ki-67