DIFFERENTIAL EFFECT OF THE TETRAPEPTIDE ACSDKP ON HUMAN NORMAL AND LEUKEMIC BLOOD PROGENITORS

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), isolated from fetal calf marrow and now chemically synthetized, inhibits the entry of murine CFU-S into DNA synthesis and so protects mice against the toxicity of high doses of chemotherapy. In view of its potential clinical use as a marrow protector, we have investigated its effects on human normal and leukemic cells. The synthetic tetrapeptide reduced significantly the percentage in DNA synthesis of bone marrow progenitors CFU-GM, BFU-E and CFU-E and inhibited the colony growth by about 40% at nanomolar concentration. This inhibition was reversible and affected cycling cells. Furthermore, cord blood progenitors, which were highly cycling, were also significantly inhibited by the peptide. AcSDKP was then assayed on the peripheral blood cells from chronic myeloid leukemic (CML) patients. No change in the number nor in the percentage of progenitors in S phase was observed whatever the doses used. The leukemic origin of the colonies was confirmed by PCR analysis. Thus, the selective inhibitory effect of the peptide on normal progenitors represents a potential therapeutic advantage for marrow protection during chemotherapy.