ENFORCED EXPRESSION OF THE M-R 33,000 PIM-1 KINASE ENHANCES FACTOR-INDEPENDENT SURVIVAL AND INHIBITS APOPTOSIS IN MURINE MYELOID CELLS

Expression of the M-r 33,000 human Pim-1 protein is induced in hematop oietic cells by a variety of grolvth factors and cytokines. We have in troduced the human pim-1 cDNA via retroviral transduction into interle ukin (IL)-3-dependent FDC-P1 cells and examined the resulting phenotyp e, Compared with cells infected with a neo-encoding retrovirus (FD/neo ), cells infected with a pim-l-transducing virus (IL)-3-dependent FDC- P1 cells and examined the resulting phenotype. Compared with cells inf ected with a neo-encoding retrovirus (FD/neo), cells infected with a p im-1-transducing virus (FD/hpim) showed longer survival or autonomous growth in suspension culture in the absence of IL-3, as well as IL-3-i ndependent clonogenic growth in semisolid medium. The unique murine M- r 44,000 Pim-1 protein, as well as human proteins with short C- or N-t erminal truncations, also was biologically active. This effect of Pim- 1 expression was associated with a decrease in apoptotic cells and an increase in G(0)/G(1)-phase cells, and the increase in G(0)/G(1)-phase cells caused by enforced expression of Pim-1 was due to a checkpoint. The Pim-1 kinase appears to function primarily as a survival factor i n factor-dependent FDCP-1 cells subjected to either cytokine withdrawa l or exposure to cytotoxic agents.