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

P. Jane Owen-Lynch, Julie A. Adams, Michelle L. Brereton, Lloyd G. Czaplewski, Anthony D. Whetton, John A. Liu Yin

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Abstract

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.
LanguageEnglish
Pages77-84
Number of pages8
JournalBritish Journal of Haematology
Volume95
Issue number1
DOIs
Publication statusPublished - 1 Oct 1996
Externally publishedYes

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Chemokine CCL3
Chemokines
Acute Myeloid Leukemia
Thymidine
Conditioned Culture Medium
Intercellular Signaling Peptides and Proteins
Stem Cell Factor
Cytokines
Macrophage Inflammatory Proteins
Growth Inhibitors
Methylcellulose
Granulocyte-Macrophage Colony-Stimulating Factor
Recombinant Proteins

Cite this

Owen-Lynch, P. Jane ; Adams, Julie A. ; Brereton, Michelle L. ; Czaplewski, Lloyd G. ; Whetton, Anthony D. ; Liu Yin, John A. / The effect of the chemokine rhMIP-1α, and a non-aggregating variant BB-10010, on blast cells from patients with acute myeloid leukaemia. In: British Journal of Haematology. 1996 ; Vol. 95, No. 1. pp. 77-84.
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abstract = "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.",
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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. / Owen-Lynch, P. Jane; Adams, Julie A.; Brereton, Michelle L.; Czaplewski, Lloyd G.; Whetton, Anthony D.; Liu Yin, John A.

In: British Journal of Haematology, Vol. 95, No. 1, 01.10.1996, p. 77-84.

Research output: Contribution to journalArticle

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T1 - The effect of the chemokine rhMIP-1α, and a non-aggregating variant BB-10010, on blast cells from patients with acute myeloid leukaemia

AU - Owen-Lynch, P. Jane

AU - Adams, Julie A.

AU - Brereton, Michelle L.

AU - Czaplewski, Lloyd G.

AU - Whetton, Anthony D.

AU - Liu Yin, John A.

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AB - 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.

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