Preprint Article Version 1 This version is not peer-reviewed

The CXCR4-CXCL12-Axis is of Prognostic Relevance in DLBCL and Its Antagonists Exert Pro-Apoptotic Effects in Vitro

Version 1 : Received: 30 July 2019 / Approved: 31 July 2019 / Online: 31 July 2019 (11:05:51 CEST)

How to cite: Pansy, K.; Feichtinger, J.; Ehall, B.; Uhl, B.; Sedej, M.; Roula, D.; Pursche, B.; Wolf, A.; Zoidl, M.; Steinbauer, E.; Gruber, V.; Greinix, H.; Prochazka, K.; Thallinger, G.; Heinemann, A.; Beham-Schmid, C.; Neumeister, P.; Wrodnigg, T.; Fechter, K.; Deutsch, A. The CXCR4-CXCL12-Axis is of Prognostic Relevance in DLBCL and Its Antagonists Exert Pro-Apoptotic Effects in Vitro. Preprints 2019, 2019070352 (doi: 10.20944/preprints201907.0352.v1). Pansy, K.; Feichtinger, J.; Ehall, B.; Uhl, B.; Sedej, M.; Roula, D.; Pursche, B.; Wolf, A.; Zoidl, M.; Steinbauer, E.; Gruber, V.; Greinix, H.; Prochazka, K.; Thallinger, G.; Heinemann, A.; Beham-Schmid, C.; Neumeister, P.; Wrodnigg, T.; Fechter, K.; Deutsch, A. The CXCR4-CXCL12-Axis is of Prognostic Relevance in DLBCL and Its Antagonists Exert Pro-Apoptotic Effects in Vitro. Preprints 2019, 2019070352 (doi: 10.20944/preprints201907.0352.v1).

Abstract

In tumour cells of more than 20 different cancer types, the CXCR4-CXCL12-axis is involved in multiple key processes including proliferation, survival, migration, invasion, and metastasis. Since data on this axis in diffuse large B cell lymphoma (DLBCL) are inconsistent and limited, we comprehensively studied the CXCR4-CXCL12-axis in our DLBCL cohort as well as the effects of CXCR4 antagonists on lymphoma cell lines in vitro. In DLBCL, we observed a 140-fold higher CXCR4 expression compared to non-neoplastic controls. Interestingly, high expression of CXCR4 was associated with poor clinical outcome. Furthermore, in corresponding bone marrow biopsies, we observed a correlation of CXCL12 expression and lymphoma infiltration rate as well as a reduction of CXCR4 expression in remission of bone marrow involvement after treatment. Furthermore, the niacin derivate of the CXCR4 antagonist AMD070, which was synthesized by us, demonstrated stronger pro-apoptotic effects than AMD070 in vitro and induced expression of certain pro-apoptotic genes in CXCR4 positive lymphoma cell lines. Finally, WK1 treatment resulted in reduced expression of JNK-, ERK1/2- and NFκB/BCR-target genes. These data indicate that the CXCR4-CXCL12-axis impacts the pathogenesis of DLBCL and represents a potential therapeutic target in aggressive lymphomas.

Subject Areas

DLBCL; CXCR4-CXCL12-axis; CXCR4 antagonist

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