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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

Abstract: Abnormal expression of the chemokine receptor CXCR4 plays an essential role in tumor cell dissemination and disease progression.However, the significance of CXCR4 overexpressionin de nava diffuse large B cell lymphoma (DLBCL) is unknown. n 743 patfents with de novo diffuse large B celllymphoma (DLBCL) who recelved standard Rltuxlmab-CHOPimmunochemotherapy,we assessed the expression of CXCR4 and dlSHCted its prognostic signiftcenceIn various DLBCL subsets. Our results showed that CXCR4+ patients was associated wlth mala,bulky tumor,high Ki-67indax,actlvatfld B-cell-like (ABC) subtype,and Myc,Bcl-2 or p53 overexpression.Moreover, CXCR4+ was an independent factor predictlng poorer progression-free survival n germinal­ center B-cell-like (GCB)-DLBCL,but not In ABC-DLBCL; and in patients wlth an IPI of S2,but not in those with an IPl>2. The lack of prognostic signiflcance of CXCR4 In ABC-DLBCL was likely due to the actlvatlon of p53 tumor suppressor attenuatlng CXCR4 signaling. Furthermore,concurrent CXCR4+ and BCL2 translocatlon showed dlsmal outcomes resembling but lndependent of MYC/ BCL2 double-hlt DLBCL.Gene expression profiling suggested that alteratlons in the tumor microenvlronment and lmmune responses,increased tumor prollferation and survival,and the dlsseminatlon of CXCR4+ tumor cells to distant organs or tissues were underlying molecular mechanisms responsible for the CXCR4+ associated poor prognosis.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Oncotarget, 20 March 2015, Vol. 6, Nº 8, pages 5597-5614

Editorial: Impact Journals

 Fecha de publicación: 20/03/2015

Nº de páginas: 18

Tipo de publicación: Artículo de Revista

 DOI: 10.18632/oncotarget.3343

ISSN: 1949-2553

Autores/as

CHEN, JIAYU

XU-MONETTE, ZIJUN Y.

DENG, LIJUAN

SHEN, QI

MANYAM, GANIRAJU C.

MARTÍNEZ-LÓPEZ, AZAHARA

ZHANG, LI

SANTIAGO MONTES MORENO

VISCO, CARLO

TZANKOV, ALEXANDAR

YIN, LIHUI

DYBKAER, KAREN

CHIU, APRIL

ORAZI, ATTILIO

ZU, YOULI

BHAGAT, GOVIND

RICHARDS, KRISTY L.

HSI, ERIC D.

MIGUEL ANGEL PIRIS PINILLA

CHOI, WILLIAM W.L.