摘要
弥漫大B细胞淋巴瘤(DLBCL)是最常见的非霍奇金淋巴瘤,占成人淋巴瘤发病率的30%～40%。由于受预后危险因素和生物学特性的影响,不同患者的5年生存率差异很大。DLBCL的发病率呈逐年上升趋势,仅40%～45%的患者可经CHOP方案治愈,美罗华联合CHOP方案可以显著延长患者的生存期。临床工作中发现IPI评分不能准确预测DLBCL患者的预后,所以急需找到能反映其生物学行为的特异性分子指标来准确预测患者的预后并指导个体化治疗方案的制定。CDC7是一种丝氨酸/苏氨酸激酶,最早在酵母中发现,与DNA复制有关。人CDC7通过磷酸化微小染色体维持蛋白2(MCM2)来启动DNA的复制。许多恶性肿瘤细胞中存在CDC7的高表达,包括DLBCL。CDC7高表达是DLBCL患者的预后不良因素之一,可作为DLBCL的特异性预后指标指导患者预后;靶向抑制CDC7基因通路可以诱导DLBCL细胞的凋亡,与美罗华联合有协同增效作用。CDC7和MCM2在指导DLBCL的预后及临床治疗方面具有重要的临床意义。CDC7基因通路可以成为治疗DLBCL患者的新的治疗靶点。CDC7抑制剂与美罗华联合可以有效提高难治性DLBCL患者的疗效。
Diffuse large B-cell lymphoma （DLBCL） is the most common form of lymphoma that accounts for 30% to 40% of all lymphomas among adults. The clinical outcomes are extremely varied, with five-year survival rates between 30% and 80%, which are widely dependent on clinical risk factors and biological heterogeneity. Based on biological heterogeneities, DLBCL can be divided into different subgroups, such as germinal center B-cell-like （GCB） DLBCL, activated B-cell-like （ABC） DLBCL, and primary mediastinal B-cell lymphoma （PMBL）. The five-year survival rates of GCB-DLBCL and ABC-DLBCL are 59% and 30%, respectively. The rituximab-combined CHOP （RCHOP） regimen has significantly improved the overall survival of DLBCL patients. However, a number of patients remain resistant to rituximab or undergo relapse after rituximab treatment. We studied the relationship between the expression level of cell division cycle 7 （CDCT） protein and the survival rate of 60 DLBCL patients in a previous study. After they received RCHOP chemotherapy, the median survival time of patients with low CDC7 expression was higher than those with high CDC7 expression （P=0.027）. Higher expression of CDC7 was observed among ABC-DLBCL patients （21/28, 75.0%）. Overall, we speculate that the CDCT/phospharylated minute chromosome maintenance protein 2 （pMCM2） signal pathway has an important role in chemotherapy resistance. CDC7 can also be a potential therapeutic target in DLBCL, especially for ABC-DLBCL. The in vitro culture system and tumor-transplanted nude mice model are used in this study to examine CDC7 gene expression. CDC7 gene expression are inhibited and enhanced in this study to clearly identify the relationship between the CDC7/pMCM2 signal pathway and the survival of DLBCL cells. Furthermore, we explore relevant clinical significance focused on the potential use of novel molecular targeting strategies against DLBCL, especially for ABC-DLBCL.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2013年第11期678-681,共4页
Chinese Journal of Clinical Oncology
