核仁素（NCL）与miR-221相互作用调控急性白血病耐药的研究

成人急性白血病（AL）复发率高，5年总生存率（OS）较低，对化疗药物产生耐药是AL治疗失败的主要原因之一。前期的预实验结果显示，核仁素（NCL）及miR-221在耐药的白血病细胞株高表达，并且复发/难治患者的阳性率也明显高于初治患者，两者间的表达呈一定程度的相关性，NCL与miR-221如何相互作用？如何影响白血病的耐药性？目前均未明了。本项目拟从患者表达水平检测、细胞体外实验及动物体内实验三大方面进行研究，采用干扰及过表达技术，以HL-60细胞及耐阿霉素的HL-60细胞(HL-60/ADR)、Molt-4及其耐阿霉素的细胞（MAR）为研究对象，观察上调/下调NCL基因及miR-221对白血病细胞耐药表型的影响，将从新的角度探讨NCL及miR-221的相互作用对白血病耐药的影响及其分子机制。为指导AL分层治疗，疗效监测、预后判断，具有重要的临床实际意义和应用价值。

Adult acute leukemia (AL) have higher relapsed rate and lower 5-year overall survival (OS). Preliminary experimental results showed that nucleolin (NCL) and miR-221 were over-expressed in resistant leukemic cell lines. Refractory or relapsed AL patients had higher positivity of miR-221 and NCL expression than newly diagnosed patients, but the exact mechanism is not yet clear. The project were be carried out from three aspects: to detect NCL/ miR-221 expression levels in AL patients, experimental studies of cell lines in vitro and of NOD/SCID mice xenograft in vivo. The project intends to use RNA interference and over-expression technology, to observe resistant phenotypes of AL cells by up-regulation/down-regulation NCL/ miR-221 in HL-60 and adriamycin-resistant HL-60 cell (HL-60/ADR)、Molt-4 and adriamycin-resistant Molt-4(MAR). The interaction between NCL and miR-221 and its involvement in drug resistance was aiso investigated. It would provide a new clue for monitoring the drug resistance and evaluating prognosis in AL.