INHIBITORY ACTIVITY OF A SYNTHETIC PENTAPEPTIDE ON LEUKEMIC MYELOPOIESIS BOTH INVITRO AND INVIVO IN RATS

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 an 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.