SNX10 regulates the proliferation, apoptosis and cell cycle of acute B lymphoblastic leukemia cells via the PI3K/Akt signaling pathway

TL;DR

This study shows that SNX10 promotes B-cell leukemia growth by activating the PI3K/Akt pathway, suggesting it could be a new treatment target.

Contribution

The study is the first to explore SNX10's role in B-ALL and links it to the PI3K/Akt pathway.

Findings

SNX10 knockdown reduced B-ALL cell proliferation and increased apoptosis.

SNX10 overexpression activated the PI3K/Akt pathway and accelerated leukemia progression in mice.

Abstract

B-cell acute lymphoblastic leukemia (B-ALL) is a type of acute lymphoblastic leukemia that originates from B cells. It typically occurs in children and adolescents, but it can also appear in adults. Sorting nexin 10 (SNX10) has recently been identified as a significant regulatory factor in various tumors, although its specific roles remain contested. However, its function in B-ALL has not been previously explored. The present study investigated the role of SNX10 in B-ALL pathogenesis. Bioinformatics analysis identified SNX10 as a Core Hub gene in the B-ALL signaling network, with significantly reduced expression in patients with B-ALL. These findings were corroborated through analysis of clinical bone marrow samples and B-ALL cell lines. Functional in vitro studies revealed that SNX10 knockdown markedly inhibited B-ALL cell proliferation, increased apoptosis, and arrested cells in the G0/G1 phase. By contrast, SNX10 overexpression enhanced cell proliferation, suppressed apoptosis and promoted G2/M phase progression. Proteomic analysis further implicated the PI3K/Akt signaling pathway in mediating the effects of SNX10. Specifically, SNX10 overexpression increased the phosphorylation levels of PI3K and Akt, while SNX10 knockdown had the opposite effect. In vivo experiments demonstrated that elevated SNX10 expression accelerated leukemia progression in a mouse model. Collectively, these findings highlighted the pivotal role of SNX10 in promoting B-ALL cell proliferation via the PI3K pathway, highlighting its potential as a therapeutic target for B-ALL and providing a foundation for future investigations.

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