OBJECTIVES: When rat chloroleukaemia (CHL) cells are grown undisturbed in a confined space, a genomic long interspersed nuclear element (LINE) is transcriptionally activated at a relatively low population density, followed by the retrotransposition of LINE and population death. This death programme is fundamentally different from conventional cell death pathways.

MATERIALS AND METHODS: This work is essentially based on the re-analysis of relevant, old experimental data. Elemental analysis of a highly purified, long-stored inhibitor sample was performed. Genomic sequence searches were performed using the basic local alignment search tool (BLAST).

RESULTS: This death programme is initiated by an endogenous inhibitor secreted by CHL cells. The inhibitor is almost certainly identical to the pentapeptide pyroGlu-Glu-Asp-Cys-Lys, shown to be a cell line-specific inhibitor of normal granulocytic cells. The inhibitor is derived from a highly conserved short open reading frame in mammalian genomes.

CONCLUSIONS: Although spontaneous population death may be a biological oddity restricted to rat CHL cells, we suggest that this death programme is responsible for the eradication of cancer cells following treatment with an inhibitor administered exogenously.

Rytömaa T, Grip-rytömaa K. Spontaneous death of rat chloroleukaemia cells induced by an endogenous growth inhibitor. Cell Prolif. 2018;51(1)

The synthetic pentapeptide pGlu-Glu-Asp-Cys-Lys has recently been proposed as the active component of a granulocyte-derived inhibitor of normal haematopoiesis. We investigated its biological activity on leukaemic myelopoiesis both in vitro and in vivo in rats. Three different human permanent myeloid leukaemic cell lines (HL60, KG1, ML3) and a rat transplantable acute myeloid leukaemia (Shay leukaemia) were studied. Neither HL60 nor KG1 were sensitive to the peptide whereas a consistently reproducible inhibition of 3H-TdR uptake was observed in ML3 cells. This effect was not due to a unspecific toxic action on target cells and was spontaneously reversible. When injected i.p. twice daily at an appropriate concentration in rats bearing Shay leukaemia, the peptide caused a significant increase in survival. Our results therefore indicate that the synthetic pentapeptide studied inhibits not only normal but also leukaemic myelopoiesis.

Foa P, Chillemi F, Lombardi L, Lonati S, Maiolo AT, Polli EE. Inhibitory activity of a synthetic pentapeptide on leukaemic myelopoiesis both in vitro and in vivo in rats. Eur J Haematol. 1987;39(5):399-403.