Objective To investigate the effects of tumor necrosis factor-α (TNF-α) on the malignant biological behavior of B-cell acute lymphoblastic leukemia (B-ALL) and its underlying mechanisms.

Methods Plasma TNF-α levels were measured by chemiluminescence in 124 patients with B-ALL, 25 healthy controls, and 77 patients with other hematologic diseases. Transcriptome sequencing was performed to analyze gene expression changes in primary B-ALL cells after TNF-α treatment. Transwell assays, ELISA, and RT-qPCR were then used to evaluate the effects of TNF-α on the migration and invasion of Nalm-6 cells and on MMP-10 expression. Finally, the prognostic significance of TNF-α and MMP-10 was assessed in conjunction with clinical data.

Results Bone marrow plasma TNF-α levels were higher in patients with B-ALL than in the control group, with mean ranks of 90.61 and 51.22, respectively (P < 0.05), and were negatively associated with chemotherapy remission. TNF-α significantly upregulated MMP-10 expression through activation of the MAPK signaling pathway (P < 0.01) and enhanced the migration and invasion of B-ALL cells (P < 0.001). Clinical analysis showed that: 1) patients with central nervous system leukemia (CNSL) had higher bone marrow plasma MMP-10 levels than those without CNSL (720.6 pg/mL vs. 307.8 pg/mL, P < 0.0001); 2) MMP-10 levels were higher in patients with Ph-positive disease, high white blood cell counts, or non-remission after chemotherapy (all P < 0.05); and 3) patients with high bone marrow plasma MMP-10 levels had significantly shorter leukemia-free survival (P = 0.0334).

Conclusion The TNF-α/MAPK/MMP-10 axis promotes B-ALL progression, and MMP-10 may serve as both a prognostic biomarker and a potential therapeutic target.