# IL-1β Controls Proliferation, Apoptosis, and Necroptosis Through the PI3K/AKT/Src/NF-κB Pathway in Leukaemic Lymphoblasts

## TL;DR

This study shows how the IL-1β protein influences cancer cell growth and death in leukemia through a specific signaling pathway.

## Contribution

The study identifies the PI3K/AKT/Src/NF-κB pathway as a key mechanism through which IL-1β affects leukaemic lymphoblasts.

## Key findings

- IL-1β activates the PI3K/AKT/Src/NF-κB pathway in leukaemic lymphoblasts.
- This pathway regulates cell proliferation, apoptosis, and necroptosis in these cells.
- The findings suggest that targeting this pathway could be a potential treatment for ALL.

## Abstract

Background: Chronic inflammation and the development of cancer are closely linked, with components that comprise the tumour microenvironment—including proinflammatory cytokines—exerting essential tumourigenic effects. These proinflammatory cytokines include IL-1β, which has been reported to be overexpressed in several cancers and shown to activate several signalling pathways. These pathways may involve kinases such as AKT (serine/threonine kinase) and Src (Proto-oncogene tyrosine-protein kinase), and have a broad capacity to activate nuclear factors, including NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells), which can regulate the transcription of genes encoding proteins such as cIAP1 (Cellular Inhibitor of Apoptosis Protein 1), Bcl-2 (B-cell lymphoma 2), and cyclin D1, thereby regulating processes like apoptosis and cell cycle inhibition. Objectives: The aim of this study was to investigate the role of IL-1β (Interleukin-1 beta) in regulating cell death and proliferation in RS4:11 leukaemic lymphoblasts via the PI3K (Phosphoinositide 3-kinase)/AKT/Src/NF-κB pathway using an in vitro experimental approach. Methods: We employed flow cytometry to determine the expression levels and phosphorylation status of various proteins; proliferation was assessed using the CCK-8 kit, and apoptosis was evaluated with the Annexin V kit. Results: Our findings indicate that the IL-1β-activated signalling pathway modulates these cellular processes in leukaemic lymphoblasts. Conclusions: We therefore conclude that IL-1β exerts significant effects on cell death and proliferation in leukaemic lymphoblasts through the PI3K/AKT/NF-κB pathway, with the study’s findings indicating that an inflammatory environment may promote such lymphoblasts to acquire neoplastic characteristics. As such, the proteins involved in the effects evaluated in this work could be considered as potential therapeutic targets for the treatment of Acute Lymphoblastic Leukaemia (ALL).