The inhibitory effect of human macrophage inflammatory protein-1 alpha (LD78) on acute myeloid leukemia cells in vitro.

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has recently been shown to inhibit proliferation of immature hemopoietic progenitors. In addition, significant inhibition of early and mature leukemic progenitors in acute myeloid leukemia (AML) has been obtained with MIP-1 alpha. We performed a study of 25 AML patients at diagnosis to evaluate the effect of a human homolog of MIP-1 alpha (LD78) on bone marrow (BM) and peripheral blood (PB) leukemic progenitors (colony-forming unit-AML [CFU-AML]) and AML cell proliferation. A methylcellulose culture system was used for CFU-AML and incorporation of 3H-TdR for AML cell proliferation. We found that LD78 inhibits CFU-AML colony formation up to 100% for the BM in 14/16 samples studied with the average maximal inhibition of 62.7 +/- 9.1% and up to 100% for the PB in 12/13 samples studied with the average maximal inhibition of 71.4 +/- 9.9%. In addition to this, LD78 inhibited AML cell proliferation up to 60% for the BM in 10/18 samples studied with the average maximal inhibition of 17.8 +/- 3.5%, and up to 87.1% for the PB cell proliferation in 10/16 samples studied with the average maximal inhibition of 27.5 +/- 6.8%. Our results have shown 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.