RIBOSOMAL-PROTEINS SUSTAIN MORPHOLOGY, FUNCTION AND PHENOTYPE IN ACUTE MYELOID-LEUKEMIA BLASTS

Translation of mRNA is a prerequisite for cell proliferation, differen tiation and viability. We have studied the effect of ribosome protein factors (GPRE) on acute myeloid leukemia (AML) blast cells. Ribosomes were isolated from MPC-11 cells using ultra-centrifugation. GPRE were extracted using a high KCl procedure. Blast cells from six AML patient s were grown in suspension cultures for 24 and 96 h. GPRE or granulocy te macrophage-colony stimulating factor (GM-CSF) were added at the sta rt of the incubation. GPRE, but not GM-CSF, prevented chromatin conden sation and fragmentation of blast cell nuclei in AML-M2, -M4 and -M5 a nd the loss of nucleoli in AML-M2 and -M5. The fraction of phagocytosi ng blast cells in AML-M1, -M2, -M4 and -M5 was increased by GPRE. GPRE stimulated opsonin-dependent and -independent attachment and internal isation of N. meningitis. GPRE increased the fraction of blasts expres sing CD11b and CD32 in AML-M2 and -M5. GPRE diminished the fraction of AML-MS cells bearing CD35 and CD32. GPRE also decreased the fraction of CD11c-bearing AML-M2 and -M5 cells. GPM-CSF potentiated effects of GPRE in AML-M1, -M2, -M4 and -M5. GPRE and GM-CSF in combination affec ted phagocytosis and surface antigen expression in blast cells that we re not influenced by either factor alone. Neither GPRE nor GM-CSF indu ced terminal differentiation or DNA-synthesis. We conclude that GPRE a ffects AML blast cell morphology, function and surface molecule expres sion, possibly by inhibiting apoptosis. The effects of GPRE may be med iated by ribosomal proteins that regulate translation and modulate the subcellular distribution of mRNA species. (C) 1998 Elsevier Science L td. All rights reserved.