Expression of interleukin-6 (IL-6) receptor gene in acute myeloblastic leukemia and response of leukemic cells to exogenous IL-6. A comparative study between cell line cells and corresponding native cells.
As interleukin (IL-6) ahs been reported to have diverse effects on acute myeloblastic leukemia (AML) blast cell growth, we investigated whether the level of IL-6 receptor (IL-6R) expression by blast cells is associated with their susceptibility to proliferate in response to exogenous IL-6. For absolute quantification of IL-6R transcript numbers, we established a quantitative IL-6R reverse transcription polymerase chain reaction (RT-PCR) method with an internal RNA standard. In the present work, two types of AML blast cells were investigated, namely autonomously growing cell line cells (n = 8) and non cultured native blast cells (n = 20), including those from which the cell lines originate. The native blast cells expressed an average of 2.8 x 10(7) +/- 1.9 x 10(7) IL-6R transcripts in one microgram of total cellular RNA, whereas the expression by the cell line cells was significantly more abundant, the value being 8.3 x 10(7) +/- 2.8 X 10(7) (P < 0.001). The proliferation responses were evaluated by exposing the cells to IL-6 (1000 U/ml) in a clonogenic cell culture assay and, in the case of the cell line cells, in a long-term suspension culture assay as well. None of the autonomously growing cell lines responded to exogenous IL-6, whereas the native blast cell showed either stimulatory, inhibitory or neutral responses. Thus, the IL-6R expression level did not predict whether the cells proliferated in response to exogenous IL-6, which shows that IL-6R quantification cannot be used as a screening test prior to possibly applying this cytokine to clinical use in AML therapy.
Department of Clinical Chemistry, University of Oulu, Finland.
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Säily
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Koistinen
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Savolainen
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Rantala
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Savolainen
D000293:Adolescent; D000328:Adult; D000368:Aged; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019947:Receptors, Interleukin-6