NPM B23在急性淋巴细胞白血病耐药中作用的研究

与儿童ALL相比，成人ALL疗效差，复发率高，5年OS低。不像AML已有大量的关于NPM基因突变的报道，NPM在ALL的表达及临床意义，与复发耐药的相关性如何？国际上则未见报道。前期在国家自然科学基金（项目号：30572132）资助下，我们开展了急性白血病蛋白质组学研究，发现NPM B23在耐药白血病细胞株高表达，初发ALL B23阳性率为54.5%，在难治和复发病人阳性率明显高于初诊病人。这是国际上首次报道难治复发ALL病人高表达B23。且发现B23蛋白高表达与NPM1 突变存在不一致性，可能提示不同的预后意义。在此基础上，本项目将延续和深入研究，通过临床与基础两方面进行研究，以阐明NPM B23蛋白在ALL耐药及其发生中的作用，探讨其与预后的相关性，将NPM B23 作为MRD检测指标和预后判断指标，指导ALL分层治疗，对克服临床耐药、提高疗效，具有重要的临床实际意义和应用价值。

Comparing to childhood acute lymphoblastic leukemia(ALL),adult ALL patients have poorer prognosis and higher relapsed rate.Nucleophosmin(NPM) mutation was widely studied in acute myeloid leukemia(AML). AML patients with sole NPM mutation would have favorable prognosis.In ALL,NPM expression and its clinical relationship to relapse or resistance have not yet been investigated.With the support of NFSC grant,we used proteomic analysis in acute leukemia and found that NPM B23 was over-expressed in resistant leukemic cell lines.Refractory or relapsed patients had higher positivity of NPM B23 expression than de novo patients.54.5% newly diagnosed ALL patients had positive expression of NPM B23.This was the first report on higher B23 expression in relapsed or refractory leukemia patients.No NPM mutation was noted in ALL.Expression of B23 detected by western blot was not found to be consistent to NPM1 mutation,suggesting a dissociation between protein and transcript expression.Based on the above results, we will carry out further clinical and basic studies to verify the role of B23 in resistance in ALL and its relationship to prognosis.