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The effect of the chemokine rhMIP‐1α, and a non‐aggregating variant BB‐10010, on blast cells from patients with acute myeloid leukaemia
Author(s) -
OwenLynch P. Jane,
Adams Julie A.,
Brereton Michelle L.,
Czaplewski Lloyd G.,
Whetton Anthony D.,
Liu Yin John A.
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.7312349.x
Subject(s) - chemokine , thymidine , alpha (finance) , growth factor , microbiology and biotechnology , recombinant dna , biology , myeloid , precursor cell , immunology , in vitro , chemistry , biochemistry , medicine , immune system , gene , construct validity , receptor , nursing , patient satisfaction
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 [ 3 H]thymidine incorporation index assay, the response of autonomous and growth factor responsive AML blast cells to the chemokine rhMIP‐1 was measured. In the case of autonomous proliferators, rhMIP‐1α had no inhibitory effect on [ 3 H]thymidine incorporation and in 4/6 cases [ 3 H]‐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 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‐1α significantly inhibited [ 3 H]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.