40 - Modulation of Acute Myeloid Leukaemic Cell Growth by Human Macrophage Inflammatory Protein-1α

Abstract

This chapter presents a study in which the effect of the peptide LD78 (the human homologue of murine macrophage inflammatory protein-1α (MIP-1α) that shows 747 amino acid sequence homology with MIP-1α) on bone marrow acute myeloid leukemia (AML) progenitor cells as measured by in vitro CFU-AML growth is investigated. The results demonstrate the inhibitory effect of LD78 on AML cell growth of bone-marrow-derived progenitors, probably mediated by an effect on AML cell proliferation. This suggests that the normal inhibitory control mechanisms mediated by LD78 are still intact in AML progenitor cells. The observed inhibitory effect of LD78 in CFU-AML growth was not related to the type of AML as evaluated by the FAB criteria for classification of AML. The effect of MIP-1α on the proliferation of T-lymphocytes seems to be mediated in part by the inhibition of IL-2 production. The study demonstrates that LD78 is more active on AML progenitors than on AML cell proliferation. Inhibition of the AML cells, although less than that of the progenitors, indicates that more limited activity of LD78 on more mature leukemic cells is present in AML.