POTENTIATED MATURATION WITH A HIGH PROLIFERATING ACTIVITY OF ACUTE PROMYELOCYTIC LEUKEMIA INDUCED IN-VITRO BY GRANULOCYTE OR GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTORS IN COMBINATION WITH ALL-TRANS-RETINOIC ACID/

All-trans retinoic acid (ATRA) induces differentiation of acute promye locytic leukemia (APL), but the effect of cytokines regulating myeloid differentiation on ATRA-induced APL cells is poorly understood. In th is study, maturation and proliferation of fresh APL cells were examine d when induced in vitro by granulocyte or granulocyte/macrophage colon y stimulating factors (G-CSF or GM-CSF) in combination with ATRA. APL cells showed a low proliferating activity when induced by ATRA alone. In contrast, cells induced by G-CSF or GM-CSF alone showed increased D NA syntheses, the levels of which were not significantly affected by t he combination of ATRA with CSFs. Interestingly, G-CSF or GM-CSF poten tiated the capability of ATRA-induced cells to reduce nitroblue tetraz olium (NBT), while G-CSF or GM-CSF alone induced no NBT reduction. Fur thermore, in several patients examined, APL cells induced by ATRA with G-CSF showed an increased activity of chemotaxis and CD11a expression . These findings suggest that G-CSF or GM-CSF can potentiate different iation of ATRA-induced APL cells while stimulating their proliferating activity as well, and that G-CSF, rather than GM-CSF, may be a useful adjunct to promote ATRA-induced differentiation of APL.