Inhibition of Normal Murine Hematopoiesis by Leukemic Cells

Abstract

Inhibition of normal mouse hemopoietic stem cells by leukemic cells (C1498) was observed with use of in vitro agar and in vivo diffusion-chamber cultures. The C1498 cells were unresponsive to colony-stimulating activity, and, above a critical threshold, they inhibited normal granulocyte progenitors in agar culture. C1498 cells added to normal marrow in diffusion chambers progressively reduced granulocyte progenitors. The larger, more rapidly growing, C1498 cells showed the most inhibitory effect. Transmembrane culture of C1498 cells adjacent to normal marrow in double diffusion chambers for five to 14 days led to reduction of recovery of granulocyte progenitors (72 +/- 7 per cent of control) and pluripotent stem cells (45 +/- 7 per cent of control) from the normal marrow chambers. These results indicate that leukemic mouse cells inhibit normal mouse-marrow stem cells by releasing a diffusible substance, and this inhibition occurs primarily at the level of the pluripotent stem cell.