核仁磷酸蛋白基因(nucleophosmin,NPM1)突变是目前急性髓系白血病发生突变率最高的基因改变,与白血病的发生发展密切相关。为探讨NPM1突变对白血病细胞体外侵袭能力的影响,将载体pEGFPC1-NPM1-mA转染THP-1白血病细胞系,筛选稳定表达NPM A型突变蛋白(NPM1-mA)的白血病细胞株(THP-1-mA)。通过transwell迁移实验、Matrigel侵袭实验以及细胞粘附实验来观察THP-1-mA细胞体外浸润转移能力的改变。结果发现,THP-1-mA细胞的体外迁移能力和侵袭能力明显高于亲代THP-1细胞;此外,THP-1-mA细胞对纤维连接蛋白的粘附能力也显著高于THP-1细胞。因此,我们的研究结果提示,NPMI突变可增强白血病细胞的体外侵袭能力,这有利于进一步明确NPM1突变基因在白血病细胞恶性转化中的调控作用。
Nucleophosmin(NPM1) mutations have been recently identified as the most frequent genetic alterations in acute myeloid leukemia and are relationship with leukemiagenesis.To explore the role of NPM1 mutations in the invasion of leukemia,the pEGFPC1-NPM1-mA plasmid vector with NPM1 mutation A(NPM1-mA) was transfected into THP-1 cells,and the leukemic cells with stably expressed NPM1-mA protein(THP-1-mA) were established.Transwell migration assay,Matrigel invasion assay and cell adhesion assay were performed.These results showed that both invasion and migratory capacities of THP-l-mA cells were much higher compared with parent THP-1 cells.In addition,THP-1-mA cells displayed higher adhesion to fibronectin compared with THP-1 cells.Therefore,our findings indicate that NPM1 mutations enhance the invasion potential of leukemic cells in vitro, which makes a further understanding of NPM1 mutations in the malignant transformation of leukemic cells.