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P38 MAPK/AKT signalling is involved in IL-33-mediated anti-apoptosis in childhood acute lymphoblastic leukaemia blast cells.

Abstract：

BACKGROUND:Acute lymphoblastic leukaemia (ALL) is often characterized by broad clinical and biological heterogeneity, as well as recurrent genetic aberrations. Despite remarkable improvements in the treatment outcome in paediatric ALL over the past several decades, it remains a leading cause of morbidity and mortality among children. Cytokines have been extensively studied in haematologic diseases; however, the mechanisms by which cytokines contribute to ALL pathogenesis remain poorly understood. METHODS:IL-33 levels were measured by enzyme-linked immunosorbent assay (ELISA). IL1RL1 expression on ALL cell surface was accessed by flow cytometry. Expression of phosphorylated p38 MAPK, p38, pAKT, AKT and GAPDH were quantified by western blot. Cell survival signals were evaluated by apoptosis using flow cytometry. RESULTS:BM samples from ALL patients at diagnosis upregulated their cell surface expression of IL1RL1, and a higher interleukin (IL)-33 level in the serum was observed as compared to the healthy individuals. Moreover, exogenous IL-33 treatment significantly inhibited apoptosis by activating p38 mitogen-activated protein kinase (MAPK) and AKT pathway, while the inhibitor for p38 MAPK, SB203580, counteracted IL-33-induced anti-apoptosis via inactivation of p38 MAPK and AKT. Furthermore, IL-33 negatively regulates cyclin B1 protein level while increasing the expression of CDK1, with SB203580 inhibiting the effect. CONCLUSION:Our study reveals an important role for IL-33/IL1RL1 axis in supporting ALL which may represent a novel treatment for paediatric patients.KEY MESSAGESBoth IL-33 and IL1RL1 levels are upregulated in primary ALL samples.IL-33 increased both p38 MAPK and AKT activation in ALL.IL-33 promotes survival and cell cycle progression of ALL cells via activating p38 MAPK.

journal_name

Ann Med

journal_title

Annals of medicine

authors

Wang Y,Hou H,Liang Z,Chen X,Lian X,Yang J,Zhu Z,Luo H,Su H,Gong Q

doi

10.1080/07853890.2021.1970217

keywords:

["AKT","ALL","IL-33","IL1RL1","P38 MAPK","anti-apoptosis"]

subject

Has Abstract

pub_date

2021-12-01 00:00:00

pages

1461-1469

issue

eissn

0785-3890

issn

1365-2060

journal_volume

pub_type

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P38 MAPK/AKT signalling is involved in IL-33-mediated anti-apoptosis in childhood acute lymphoblastic leukaemia blast cells.