Dysregulated CXCR4 expression promotes lymphoma cell survival and independently predicts disease progression in germinal center B-cell-like diffuse large B-cell lymphoma.
Dysregulated CXCR4 expression promotes lymphoma cell survival and independently predicts disease progression in germinal center B-cell-like diffuse large B-cell lymphoma.
复制标题
DOI：
10.18632/oncotarget.3343
复制
发表时间：
2015-03-20
期刊：
影响因子：
--
通讯作者：
Young KH
中科院分区：
文献类型：
--
作者：
Chen J;Xu-Monette ZY;Deng L;Shen Q;Manyam GC;Martinez-Lopez A;Zhang L;Montes-Moreno S;Visco C;Tzankov A;Yin L;Dybkaer K;Chiu A;Orazi A;Zu Y;Bhagat G;Richards KL;Hsi ED;Choi WW;van Krieken JH;Huh J;Ponzoni M;Ferreri AJ;Zhao X;Møller MB;Farnen JP;Winter JN;Piris MA;Pham L;Young KH
趋化因子受体CXCR 4的异常表达在肿瘤细胞播散和疾病进展中起重要作用。然而，CXCR 4过表达在原发弥漫性大B细胞淋巴瘤（DLBCL）中的意义尚不清楚。在743例接受标准Rituximab-CHOP免疫化疗的原发弥漫性大B细胞淋巴瘤（DLBCL）患者中，我们评估了CXCR 4的表达，并分析了其在各种DLBCL亚群中的预后意义。我们的研究结果表明，CXCR 4+患者与男性，巨大的肿瘤，高Ki-67指数，活化的B细胞样（ABC）亚型，Myc，Bcl-2或p53过表达。此外，CXCR 4+是预测生殖中心B细胞样（GCB）-DLBCL无进展生存期较差的独立因素，但在ABC-DLBCL中并非如此; IPI ≤2的患者中，但在IPI>2的患者中并非如此。CXCR 4在ABC-DLBCL中缺乏预后意义可能是由于p53肿瘤抑制因子的激活减弱了CXCR 4信号传导。此外，同时发生的CXCR 4+和BCL 2易位显示出类似于但独立于MYC/BCL 2双重打击DLBCL的令人沮丧的结果。基因表达谱分析表明，肿瘤微环境和免疫反应的改变，增加肿瘤增殖和生存，以及CXCR 4+肿瘤细胞向远处器官或组织的传播是CXCR 4+相关不良预后的潜在分子机制。
Abnormal expression of the chemokine receptor CXCR4 plays an essential role in tumor cell dissemination and disease progression. However, the significance of CXCR4 overexpression in de novo diffuse large B cell lymphoma (DLBCL) is unknown. In 743 patients with de novo diffuse large B cell lymphoma (DLBCL) who received standard Rituximab-CHOP immunochemotherapy, we assessed the expression of CXCR4 and dissected its prognostic significance in various DLBCL subsets. Our results showed that CXCR4+ patients was associated with male, bulky tumor, high Ki-67 index, activated B-cell-like (ABC) subtype, and Myc, Bcl-2 or p53 overexpression. Moreover, CXCR4+ was an independent factor predicting poorer progression-free survival in germinal-center B-cell-like (GCB)-DLBCL, but not in ABC-DLBCL; and in patients with an IPI of ≤2, but not in those with an IPI>2. The lack of prognostic significance of CXCR4 in ABC-DLBCL was likely due to the activation of p53 tumor suppressor attenuating CXCR4 signaling. Furthermore, concurrent CXCR4+ and BCL2 translocation showed dismal outcomes resembling but independent of MYC/BCL2 double-hit DLBCL. Gene expression profiling suggested that alterations in the tumor microenvironment and immune responses, increased tumor proliferation and survival, and the dissemination of CXCR4+ tumor cells to distant organs or tissues were underlying molecular mechanisms responsible for the CXCR4+ associated poor prognosis.
登录
查看更多内容
影响因子：
2.7
作者：
Ko, Sun-Young;Park, Chan-Jeoung;Chi, Hyun-Sook
通讯作者：
Chi, Hyun-Sook
影响因子：
8
作者：
Mehta, S. A.;Christopherson, K. W.;Nakshatri, H.
通讯作者：
Nakshatri, H.
DOI：
10.1073/pnas.1101133108
发表时间：
2011-10-25
影响因子：
11.1
作者：
Drury, Luke J.;Ziarek, Joshua J.;Dwinell, Michael B.
通讯作者：
Dwinell, Michael B.
影响因子：
32.4
作者：
Bannard O;Horton RM;Allen CD;An J;Nagasawa T;Cyster JG
通讯作者：
Cyster JG
影响因子：
4.4
作者：
Caron, Gersende;Le Gallou, Simon;Fest, Thierry
通讯作者：
Fest, Thierry