THE EFFECT OF THE CHEMOKINE RHMIP-1-ALPHA, AND A NON-AGGREGATING VARIANT BB-10010, ON BLAST CELLS FROM PATIENTS WITH ACUTE MYELOID-LEUKEMIA

The effects of recombinant macrophage inflammatory protein 1 alpha (rh MIP-1 alpha) on the proliferation of leukaemic blast cells from patien ts with acute myeloid leukaemia was assessed. Using the previously des cribed [H-3]thymidine incorporation index assay, the response of auton omous and growth factor responsive AML blast cells to the chemokine rh MIP-1 alpha was measured. In the case of autonomous proliferators, rhM IP-1 alpha had no inhibitory effect on [H-3]thymidine incorporation an d in 4/6 cases [H-3]- thymidine incorporation was stimulated by rhMIP- 1 alpha. In the presence of stem cell factor (SCF), a majority (8/9) o f the samples which responded to this growth factor were was included in the assay were obtained with GM-CSF-responsive samples; however, wh en these two cytokines were combined, only 3/14 were significantly inh ibited. In the presence of human placental conditioned medium (HPCM), rhMIP-1 alpha significantly inhibited [H-3]thymidine incorporation in only 2/10 of HPCM-responsive samples. In methylcellulose assays rhMIP- 1 alpha had no consistent effect on colony/cluster formation in the pr esence of either GM-CSF+SCF or HPCM. Similar results were obtained wit h BB-10010. a mutant of rhMIP-1 alpha which has defined aggregation pr operties in solution. These data suggest that autonomously proliferati ng AML cells, and also some AML samples which require cytokines to pro liferate, are non-responsive to the growth inhibitors rhMIP-1 alpha an d BB-10010 in the presence of multiple growth factors.