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Signaling through interleukin‐6 receptor supports blast cell proliferation in acute myeloblastic leukemia
Author(s) -
Säily Marjaana,
Koistinen Pirjo,
Zheng Aiping,
Savolainen EevaRiitta
Publication year - 1998
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1998.tb01083.x
Subject(s) - cytokine , cell growth , biology , glycoprotein 130 , acute myeloblastic leukemia , cell culture , receptor , clonogenic assay , cancer research , microbiology and biotechnology , immunology , interleukin 6 , leukemia , biochemistry , genetics
The role of the interleukin‐6/interleukin‐6 receptor (IL‐6/IL‐6R) system in regulating blast cell growth in 8 acute myeloblastic leukemia (AML) patient‐derived cell lines was investigated. As they all expressed IL‐ 6R and as none of them responded to exogenous IL‐6 under conventional serum‐supplemented culture conditions, we investigated whether signaling through IL‐6R plays any role in maintaining their spontaneous colony growth. This was done by treating the cells with monoclonal antibodies made against the ligand‐specific IL‐6R α‐chain or the signal transducer gp130. In serum‐supplemented cultures inhibition of gp 130 function did not affect the cell line growth, whereas anti‐IL‐6R α‐chain antibody reduced colony growth. While some of the cell lines also showed similar growth characteristics in a serum‐free environment, some others changed their growth pattern and stopped responding to anti‐IL‐6R α‐chain treatment. At the same time, these cell lines also began to respond to exogenously added IL‐6 and, interestingly, were stimulated by anti‐gp130 antibody. Hence, in some of the blast cells, clonogenic cell growth seemed to be also negatively controlled by an endogenously produced growth‐depressing cytokine or cytokines that utilize gp130. All the cell lines, whether cultured in the presence or absence of serum expressed IL‐6 both at mRNA and protein level. The current results indicate that AML cells can use IL‐6 as a growth stimulating factor, supplied either paracrinely or autocrinely. This could implicate the use of anti‐IL‐6R α‐chain antagonists in AML treatment, not IL‐6.