The effect of the chemokine rhMIP-1 alpha, and a non-aggregating variant BB-10010, on blast cells from patients with acute myeloid leukaemia.
The effects of recombinant macrophage inflammatory protein 1 alpha (rhMIP-1 alpha) 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-1 alpha was measured. In the case of autonomous proliferators, rhMIP-1 alpha had no inhibitory effect on [3H]thymidine incorporation and in 4/6 cases [3H]-thymidine incorporation was stimulated by rhMIP-1 alpha. 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-1 alpha was included in the assay medium. Similar results were obtained with GM-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-1 alpha significantly inhibited [3H]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 presence of either GM-CSF + SCF or HPCM. Similar results were obtained with BB-10010, a mutant of rhMIP-1 alpha 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-1 alpha and BB-10010 in the presence of multiple growth factors.
Owen-Lynch
P J
PJ
Department of Biochemistry and Applied Molecular Biology, UMIST, Manchester.
Adams
J A
JA
Brereton
M L
ML
Czaplewski
L G
LG
Whetton
A D
AD
Yin
J A
JA
D000208:Acute Disease; D002455:Cell Division / Q000187:drug effects; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor