Publications

Authors:

Chen, Jiayu; Xu-Monette, Zijun Y; Deng, Lijuan; Shen, Qi; Manyam, Ganiraju C; Martinez-Lopez, Azahara; Zhang, Li; Montes-Moreno, Santiago; Visco, Carlo; Tzankov, Alexandar; Yin, Lihui; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L; Hsi, Eric D; Choi, William W L; van Krieken, J Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J M; Zhao, Xiaoying; Møller, Michael B; Farnen, John P; Winter, Jane N; Piris, Miguel A; Pham, Lan; Young, Ken H

Title:

Dysregulated CXCR4 expression promotes lymphoma cell survival and independently predicts disease progression in germinal center B-cell-like diffuse large B-cell lymphoma

Year:

2015

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

ONCOTARGET

ISSN of journal:

1949-2553

N° Volume:

6

Number or Folder:

8

Page numbers:

5597-5614

Keyword:

BCL2; CXCR4; DLBCL; Myc; TP53 mutation; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemokine CXCL12; Cyclophosphamide; Disease Progression; Doxorubicin; Female; Gene Expression Regulation, Neoplastic; Germinal Center; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Mutation; Oligopeptides; Prednisone; Prognosis; Receptors, CXCR4; Rituximab; Transcriptome; Tumor Suppressor Protein p53; Vincristine

Short description of contents:

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.

Product ID:

107764

Handle IRIS:

11562/993478

Last Modified:

November 18, 2022

Bibliographic citation:

Chen, Jiayu; Xu-Monette, Zijun Y; Deng, Lijuan; Shen, Qi; Manyam, Ganiraju C; Martinez-Lopez, Azahara; Zhang, Li; Montes-Moreno, Santiago; Visco, Carlo; Tzankov, Alexandar; Yin, Lihui; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L; Hsi, Eric D; Choi, William W L; van Krieken, J Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J M; Zhao, Xiaoying; Møller, Michael B; Farnen, John P; Winter, Jane N; Piris, Miguel A; Pham, Lan; Young, Ken H, Dysregulated CXCR4 expression promotes lymphoma cell survival and independently predicts disease progression in germinal center B-cell-like diffuse large B-cell lymphoma «ONCOTARGET» , vol. 6 , n. 8 , 2015 , pp. 5597-5614

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