physiomolecular analysis of S100A6 in leukemia with MLL/AF4

我们发现mll - af4阳性的ALL细胞系对TNF-α具有抗性。为了研究mll - af4阳性白血病对TNF-α的耐药机制，我们重点研究了S100A6作为一个可能的因素。在TNF-α存在下，仅在mll - af4阳性的ALL细胞系中观察到S100A6表达上调和p53-caspase8-caspase 3通路的抑制。S100A6通过抑制mll - af4阳性ALL细胞株p53-caspase8-caspase 3通路对TNF-α耐药的影响也通过对S100A6的小干扰RNA分析得到证实。在先前建立的MLL-AF4转基因小鼠中也证实了这一途径。上述结果提示mll - af4阳性ALL细胞通过上调S100A6表达，进而干扰p53-caspase 8-caspase 3通路，逃避TNF-α-介导的凋亡。

We showed that MLL-AF4-positive ALL cell lines are resistant to TNF-α. To examine the mechanism of resistance to TNF-α of MLL-AF4-positive leukemia, we focused on S100A6 as a possible factor. Upregulation of S100A6 expression and inhibition of the p53-caspase8-caspase 3 pathway were observed only in MLL-AF4-positive ALL cell lines in the presence of TNF-α. The effect of S100A6 on resistance to TNF-α by inhibition of the p53-caspase8-caspase 3 pathway of MLL-AF4-positive ALL cell lines were also confirmed by analysis using small interfering RNA against S100A6. This pathway was also confirmed in previously established MLL-AF4 transgenic mice. These results suggest that MLL-AF4-positive ALL escapes from TNF-α-mediated apoptosis by upregulation of S100A6 expression, followed by interfering with p53-caspase 8-caspase 3 pathway.