An essential role for polyamine biosynthesis during human granulopoietic differentiation.

The role of polyamines during the process of colony-stimulating factor-induced proliferation and differentiation of human granulocyte-macrophage progenitor cells was studied using in vitro liquid cultures and semisolid agar cultures. Human placenta-conditioned medium, a partially purified preparation of colony-stimulating factor, rapidly and significantly increased the intracellular putrescine concentration of light-density, non-adherent, T-lymphocyte-depleted human marrow cells, Inhibition of polyamine biosynthesis with alpha-difluoromethylornithine, a catalytic, irreversible inhibitor or ornithine decarboxylase, resulted in an accumulation of blasts, promyelocytes, and myelocytes with a concomitant decrease in metamyelocytes and polymorphonuclear granulocytes, suggesting a granulopoietic differentiation block. The observed inhibition of differentiation could easily be reversed with exogenously added putrescine. These data indicate clearly an essential role for polyamines during the process of human granulopoietic differentiation.