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CXCR7 expression in diffuse large B-cell lymphoma identifies a subgroup of CXCR4+ patients with good prognosis.

ABSTRACT: The CXCR4/CXCL12 axis has been extensively associated with different types of cancer correlating with higher aggressiveness and metastasis. In diffuse large B-cell lymphoma (DLBCL), the expression of the chemokine receptor CXCR4 is involved in the dissemination of malignant B cells and is a marker of poor prognosis. CXCR7 is a chemokine receptor that binds to the same ligand as CXCR4 and regulates de CXCR4-CXCL12 axis. These findings together with the report of CXCR7 prognostic value in several tumor types, led us to evaluate the expression of CXCR7 in diffuse large B-cell lymphoma biopsies. Here, we describe that CXCR7 receptor is an independent prognostic factor that associates with good clinical outcome. Moreover, the expression of CXCR7 associates with increased survival in CXCR4+ but not in CXCR4- DLBCL patients. Thus, the combined immunohistochemical evaluation of both CXCR7 and CXCR4 expression in DLBCL biopsies may improve their prognostic value as single markers. Finally, we show that CXCR7 overexpression in vitro is able to diminish DLBCL cell survival and increase their sensitivity to antitumor drugs. Hence, further studies on the CXCR7 receptor may establish its role in DLBCL and the molecular mechanisms that modulate CXCR4 activity.

SUBMITTER: Moreno MJ

PROVIDER: S-EPMC6007902 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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CXCR7 expression in diffuse large B-cell lymphoma identifies a subgroup of CXCR4+ patients with good prognosis.

Moreno María José MJ Gallardo Alberto A Novelli Silvana S Mozos Ana A Aragó Marc M Pavón Miguel Ángel MÁ Céspedes María Virtudes MV Pallarès Víctor V Falgàs Aïda A Alcoceba Miguel M Blanco Oscar O Gonzalez-Díaz Marcos M Sierra Jorge J Mangues Ramon R Casanova Isolda I

PloS one 20180619 6

The CXCR4/CXCL12 axis has been extensively associated with different types of cancer correlating with higher aggressiveness and metastasis. In diffuse large B-cell lymphoma (DLBCL), the expression of the chemokine receptor CXCR4 is involved in the dissemination of malignant B cells and is a marker of poor prognosis. CXCR7 is a chemokine receptor that binds to the same ligand as CXCR4 and regulates de CXCR4-CXCL12 axis. These findings together with the report of CXCR7 prognostic value in several ...[more]

PMID: 29920526

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Project description:The 2016 World Health Organization classification defines diffuse large B-cell lymphoma (DLBCL) subtypes based on Epstein-Barr virus (EBV) infection and oncogenic rearrangements of MYC/BCL2/BCL6 as drivers of lymphomagenesis. A subset of DLBCL, however, is characterized by activating mutations in MYD88/CD79B We investigated whether MYD88/CD79B mutations could improve the classification and prognostication of DLBCL. In 250 primary DLBCL, MYD88/CD79B mutations were identified by allele-specific polymerase chain reaction or next-generation-sequencing, MYC/BCL2/BCL6 rearrangements were analyzed by fluorescence in situ hybridization, and EBV was studied by EBV-encoded RNA in situ hybridization. Associations of molecular features with clinicopathologic characteristics, outcome, and prognosis according to the International Prognostic Index (IPI) were investigated. MYD88 and CD79B mutations were identified in 29.6% and 12.3%, MYC, BCL2, and BCL6 rearrangements in 10.6%, 13.6%, and 20.3%, and EBV in 11.7% of DLBCL, respectively. Prominent mutual exclusivity between EBV positivity, rearrangements, and MYD88/CD79B mutations established the value of molecular markers for the recognition of biologically distinct DLBCL subtypes. MYD88-mutated DLBCL had a significantly inferior 5-year overall survival than wild-type MYD88 DLBCL (log-rank; P=0.019). DLBCL without any of the studied aberrations had superior overall survival compared to cases carrying ?1 aberrancy (log-rank; P=0.010). MYD88 mutations retained their adverse prognostic impact upon adjustment for other genetic and clinical variables by multivariable analysis and improved the prognostic performance of the IPI. This study demonstrates the clinical utility of defining MYD88-mutated DLBCL as a distinct molecular subtype with adverse prognosis. Our data call for sequence analysis of MYD88 in routine diagnostics of DLBCL to optimize classification and prognostication, and to guide the development of improved treatment strategies.

Dataset Information

CXCR7 expression in diffuse large B-cell lymphoma identifies a subgroup of CXCR4+ patients with good prognosis.

Publications

CXCR7 expression in diffuse large B-cell lymphoma identifies a subgroup of CXCR4+ patients with good prognosis.

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