Department of Morphology and Embryology and LTTA Centre, University of Ferrara, Ferrara, Italy.
Invest New Drugs. 2012 Dec;30(6):2403-6. doi: 10.1007/s10637-011-9786-2. Epub 2012 Jan 13.
The basal SOCS1 mRNA levels were significantly lower in p53(mutated) BJAB and MAVER leukemic cell lines with respect to p53(wild-type) SKW6.4 and JVM-2 leukemic cell lines, p53(wild-type) primary B chronic lymphocytic leukemia (B-CLL) cells and primary normal peripheral blood mononuclear cells (PBMC). Moreover, the MDM2 small molecule inhibitor Nutlin-3 significantly increased the levels of SOCS1 mRNA in both primary p53(wild-type) B-CLL cells as well as in p53(wild-type) B leukemic cell lines, but not in p53(mutated) B leukemic cell lines nor in primary PBMC. Of note, a significant inverse correlation was observed between SOCS1 mRNA and miR-155 levels in Nutlin-3-treated primary B-CLL cells and PBMC, suggesting that the miRNA-155/SOCS1 axis represents a potentially important therapeutic target of Nutlin-3 in B-CLL.
与 p53（野生型）SKW6.4 和 JVM-2 白血病细胞系、p53（野生型）原发性 B 慢性淋巴细胞白血病（B-CLL）细胞和原发性正常外周血单核细胞（PBMC）相比，p53（突变型）BJAB 和 MAVER 白血病细胞系中的基础 SOCS1 mRNA 水平显著降低。此外，MDM2 小分子抑制剂 Nutlin-3 显著增加了原发性 p53（野生型）B-CLL 细胞以及 p53（野生型）B 白血病细胞系中 SOCS1 mRNA 的水平，但对 p53（突变型）B 白血病细胞系和原发性 PBMC 则没有影响。值得注意的是，在经 Nutlin-3 处理的原发性 B-CLL 细胞和 PBMC 中，SOCS1 mRNA 与 miR-155 水平之间存在显著的负相关，这表明 miRNA-155/SOCS1 轴是 Nutlin-3 在 B-CLL 中潜在的重要治疗靶点。
