The effect of the chemokine rhMIP-1α, and a non-aggregating variant BB-10010, on blast cells from patients with acute myeloid leukaemia

The effects of recombinant macrophage inflammatory protein 1α (rhMIP-1α) on the proliferation of leukaemic blast cells from patients with acute myeloid leukaemia was assessed. Using the previously described [3H]thymidine incorporation index assay, the response of autonomous and growth factor responsive AML blast cells to the chemokine rhMIP-1α was measured. In the case of autonomous proliferators, rhMIP-1α had no inhibitory effect on [3H]thymidine incorporation and in 4/6 cases [3H]-thymidine incorporation was stimulated by rhMIP-1α. In the presence of stem cell factor (SCF), a majority (8/9) of the samples which responded to this growth factor were inhibited when rhMIP-1α was included in the assay medium. Similar results were obtained with CM-CSF responsive samples; however, when these two cytokines were combined, only 3/14 were significantly inhibited. In the presence of human placental conditioned medium (HPCM), rhMIP-1α significantly inhibited [3H]thymidine incorporation in only 2/10 of HPCM-responsive samples. In methylcellulose assays rhMIP-1α had no consistent effect on colony/cluster formation in the presence of either GM-CSF + SCF or HPCM. Similar results were obtained with BB-10010, a mutant of rhMIP-1α which has defined aggregation properties in solution. These data suggest that autonomously proliferating AML cells, and also some AML samples which require cytokines to proliferate, are non-responsive to the growth inhibitors rhMIP-1α and BB-10010 in the presence of multiple growth factors.