ID: 18: IL-27 promotes cell proliferation and survival of human leukemic cell lines through activation of the MAPK/ERK and PI3K/AKT signalling pathways

Abstract

IL-27 is a pleiotropic cytokine of the IL-6/IL-12 family with diverse biological functions. Previous in vivo studies have suggested the anti-tumour activities of IL-27 in animal models, whereas clinical observations indicate the link of IL-27 in tumour progression. IL-27 has recently been shown to cause inhibition of proliferation on primary leukemic cells from paediatric patients, but information on its role in human leukemic cell lines is limited. In the present study, we investigated the ability of IL-27 to regulate cell growth and survival of various human leukemic cell lines. Our results showed that in human leukemic cell lines coexpressing both IL-27R chains IL-27R α and gp130, IL-27 did not inhibit cell growth, but caused a dose-dependent proliferation of the acute myeloid leukemic cell line OCI-AML5, and the erythroleukemic cell lines, TF-1, UT-7 and UT7/EPO. Consistent with this, IL-27 promoted cell survival and reduced TNF- α -induced apoptosis of the leukemic cell lines. IL-27 also decreased the sensitivity of the leukemic cells to chemotherapeutic drugs cytarabine and daunorubicin. We observed that IL-27 induced the activation of STAT1/3 and ERK1/2 in the leukemic cells. Growth stimulation by IL-27 was suppressed by the specific MEK inhibitor U0126 and the PI3K inhibitor wortmannin, suggesting that IL-27-induced cell proliferation is mediated via the activation of two distinct pathways of MAPK/ERK and PI3K/AKT. The present study is the first demonstration of the proliferative property of IL-27 in human leukemic cell lines, suggesting that IL-27 may play an unfavourable role in tumour growth of certain subtypes of human leukaemia.