经典霍奇金淋巴瘤（cHL）H/RS细胞起源于生发中心残疾B淋巴细胞，与细胞分化阻滞相关。前期我们发现H/RS细胞株L428稳定过表达CD99后重现B细胞特性，出现浆细胞分化基因PRDM1表达，miR-9表达受抑；单独抑制miR-9也可出现PRDM1表达，由此提出一个新的诱导分化内容：即CD99调控miR-9诱导H/RS细胞向终末B细胞再分化。本项目拟增加H/RS细胞株，采用基因和miRNA转染及干扰、体内外实验，并结合蛋白组学和生物信息学进行（1）确认CD99和miR-9诱导H/RS细胞向终末B细胞再分化；（2）证实CD99通过调控miR-9/PRDM1途径发挥诱导分化作用；（3）分析检测CD99和miR-9之间的调节蛋白或通路。旨在揭示一个新的诱导H/RS细胞分化机制，为cHL的诱导分化治疗提供理论依据和精确靶标，进一步阐明H/RS细胞发生发展的机理。

H/RS cells of Classical Hodgkin lymphoma derives from the mutant and disabled B lymphocytes in germinal center. Our recent research indicated that over-expression of CD99 in L428 of H/RS cell line results in the restoration of B-cell characteristics by increasing expression of plasma cell differentiation switch gene PRDM1, and specially inhibiting the high level of miR-9 expression. Particularly inhibiting miR-9 also triggered PRDM1 expressing. Therefor, we put forward a new content about inducing differentiation,that CD99 regulates miR-9 inducing H/RS cell to terminal B cell redifferentiation.In this study, we would increase H/RS cell lines to further the research. Gene and miRNA transfection, interfering, in vitro and in vivo experiments , proteomics and bioinformatic analysis will be applied for the following purposes:（1）to confirm that CD99 and miR-9 can induce H/RS cells redifferentiation toward terminal B cells ；（2）to verify that CD99 exerts the inducing differentiation function through the pathway of modulating miR-9/PRDM1；（3）to analyse and determine the intermediate proteins or pathways between CD99 and miR-9. Our study is to reveal a new mechanism of inducing H/RS cell differentiation, provide precise targets and theory evidence for cHL therapy by inducing H/RS cell differentiation, and further clarify the pathogenesis and development of H/RS cells.