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

Publication ,  Journal Article
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 ...
Published in: Oncotarget
March 20, 2015

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.

Duke Scholars

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Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

March 20, 2015

Volume

6

Issue

8

Start / End Page

5597 / 5614

Location

United States

Related Subject Headings

  • Vincristine
  • Tumor Suppressor Protein p53
  • Transcriptome
  • Rituximab
  • Receptors, CXCR4
  • Prognosis
  • Prednisone
  • Oligopeptides
  • Mutation
  • Middle Aged
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, J., Xu-Monette, Z. Y., Deng, L., Shen, Q., Manyam, G. C., Martinez-Lopez, A., … Young, K. H. (2015). Dysregulated CXCR4 expression promotes lymphoma cell survival and independently predicts disease progression in germinal center B-cell-like diffuse large B-cell lymphoma. Oncotarget, 6(8), 5597–5614. https://doi.org/10.18632/oncotarget.3343
Chen, Jiayu, Zijun Y. Xu-Monette, Lijuan Deng, Qi Shen, Ganiraju C. Manyam, Azahara Martinez-Lopez, Li Zhang, et al. “Dysregulated CXCR4 expression promotes lymphoma cell survival and independently predicts disease progression in germinal center B-cell-like diffuse large B-cell lymphoma.Oncotarget 6, no. 8 (March 20, 2015): 5597–5614. https://doi.org/10.18632/oncotarget.3343.
Chen J, Xu-Monette ZY, Deng L, Shen Q, Manyam GC, Martinez-Lopez A, et al. Dysregulated CXCR4 expression promotes lymphoma cell survival and independently predicts disease progression in germinal center B-cell-like diffuse large B-cell lymphoma. Oncotarget. 2015 Mar 20;6(8):5597–614.
Chen, Jiayu, et al. “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, no. 8, Mar. 2015, pp. 5597–614. Pubmed, doi:10.18632/oncotarget.3343.
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 WWL, van Krieken JH, Huh J, Ponzoni M, Ferreri AJM, Zhao X, Møller MB, Farnen JP, Winter JN, Piris MA, Pham L, Young KH. Dysregulated CXCR4 expression promotes lymphoma cell survival and independently predicts disease progression in germinal center B-cell-like diffuse large B-cell lymphoma. Oncotarget. 2015 Mar 20;6(8):5597–5614.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

March 20, 2015

Volume

6

Issue

8

Start / End Page

5597 / 5614

Location

United States

Related Subject Headings

  • Vincristine
  • Tumor Suppressor Protein p53
  • Transcriptome
  • Rituximab
  • Receptors, CXCR4
  • Prognosis
  • Prednisone
  • Oligopeptides
  • Mutation
  • Middle Aged