Blocking the CXCL12/CXCR4 axis can alter the biological functions of leukaemia cells. We hypothesise that interleukin (IL)-8 and IL-6 play an important role in this process. To test this hypothesis, we established a co-culture model of leukaemia cells and bone marrow stromal cells. Treatment of cells with AMD3100, a CXCR4 antagonist, and G-CSF blocked the CXCL12/CXCR4 axis, inducing biological changes in the leukaemia cells and altering IL-8 and IL-6 levels. Subsequently, after stimulating the CXCL12/CXCR4 axis, specific pathway blockers were employed to assess the role of four candidate signalling pathways in this process. ELISA results confirmed that MG-132 (10 μm) inhibits IL-8 expression and that the NF-κB signalling pathway contributes to this effect. Moreover, treatment with Perifosine, an AKT inhibitor, inhibited IL-6 expression. In addition, changes in the NF-κB signalling pathway inhibited IL-8 expression. Treatment with SP600125, a Jun N-terminal kinase inhibitor, and Perifosine also inhibited IL-8 expression; however, this effect occurred later. IL-6 expression was also lower in the Perifosine group; hence, inhibiting the PI3K/AKT signalling pathway can reduce IL-6 expression. This process requires the participation of multiple signalling pathways to regulate IL-8 and IL-6 expression. Therefore, the associated mechanism is likely to be highly intricate, with potential cross-effects that may impact leukaemia pathogenesis. IL-6 and IL-8 are physiologically regulated by the CXCL12/CXCR4 axis, while the NF-κB and JNK/AP-1 pathways are required for IL-8 expression in T-cell acute lymphoblastic leukaemia. Accordingly, by upregulating IL-8, the bone marrow microenvironment and CXCL12/CXCR4 axis may contribute to T-cell acute lymphoblastic leukaemia pathogenesis.

阻断 CXCL12/CXCR4 轴可以改变白血病细胞的生物学功能。我们假设白细胞介素 （IL）-8 和 IL-6 在此过程中起重要作用。为了检验这一假设，我们建立了白血病细胞和骨髓基质细胞的共培养模型。用 AMD3100、一种 CXCR4 拮抗剂和 G-CSF 处理细胞可阻断 CXCL12/CXCR4 轴，诱导白血病细胞发生生物学变化并改变 IL-8 和 IL-6 水平。随后，在刺激 CXCL12/CXCR4 轴后，采用特异性通路阻滞剂来评估四种候选信号通路在此过程中的作用。ELISA 结果证实 MG-132 （10 μm） 抑制 IL-8 表达，NF-κB 信号通路有助于这种作用。此外，用 AKT 抑制剂 Perifosine 治疗可抑制 IL-6 表达。此外，NF-κB 信号通路的变化抑制了 IL-8 的表达。用 Jun N 末端激酶抑制剂 SP600125 和 Perifosine 处理也抑制了 IL-8 的表达;然而，这种影响发生在后来。Perifosine 组的 IL-6 表达也较低;因此，抑制 PI3K/AKT 信号通路可以降低 IL-6 的表达。这个过程需要多个信号通路的参与来调节 IL-8 和 IL-6 表达。因此，相关机制可能非常复杂，具有可能影响白血病发病机制的潜在交叉效应。IL-6 和 IL-8 受 CXCL12/CXCR4 轴的生理调节，而 NF-κB 和 JNK/AP-1 通路是 T 细胞急性淋巴细胞白血病中 IL-8 表达所必需的。因此，通过上调 IL-8，骨髓微环境和 CXCL12/CXCR4 轴可能有助于 T 细胞急性淋巴细胞白血病的发病机制。