慢病毒载体介导的npm1基因沉默对hl-60 k562细胞及其耐药细胞株的作用研究-effect of lentiviral vector-mediated np m1 gene silencing on hl - 60 k562 cells and their drug-resistant cell lines.docxVIP

PAGE PAGE 6 Gene silencing of nucleophosmin in HL-60 and K562 and their resistant cell lines by lentiviral-mediated RNA interference Abstract Leukemia is a group of heterogeneous hematological malignancy. The occurrence and development of this disease are closely correlated with many genetic changes, yet the precise pathogenesis is unknown . The chemotherapy is still the main treatment measures for leukemia, but relapse and refractory diseases have become a challenge to treatment success. Most of it is due to drug resistance. Within recent 30 years, as development of cytogenetics and molecular biology, a series of genes, receptor and important intracellular substances were found, which are related to pathogensis, progress and prognosis of leukemia. Targeted treatment of leukemia at molecular level and developments of novel drugs increased become research hotspots. Nucleophosmin (NPM, B23, NO38) is a multifunctional protein, mainly located in the granular zone of nucleolus. NPM takes part in lots of cellular activities, including ribosome biogenesis, centrosome duplication, and served as molecular chaperon of proteins and nucleic acid. NPM gene abnormality could induce cell malignant proliferation and cell apoptosis, which is closely related to tumorigenesis. Recent studies showed that overexpression of NPM gene was found in many kinds of solid tumor. NPM was used as a tumor marker of malignancies, such as hepatocarcinoma, gastric-carcinoma, colon carcinoma, ovarian cancer, prostate cancer. NPM gene mutations was found in AML with normal karyotype. However, the involved molecular mechanisms of NPM in the development of leukemia is unclear yet. RNA interference, with high efficiency and specificity, is a phenomenon in which the introduction of double-stranded RNA (dsRNA) into a diverse ranges of organisms and cells causes degradation of the complementary mRNA and results in gene silencing. It helps in studying certain function of related genes in leukemia, and also