Page 208 - Haematologica May 2020

L. Chen et al.
sion and adverse prognostic significance of CXCR4 stain-
ing.33,34
These observations are noteworthy because CXCR4 may
also be a relevant treatment target. There are ongoing clini- cal trials incorporating either the CXCR4 inhibitor (AMD3100, plerixafor) or a monoclonal antibody against CXCR4 (ulocuplumab) into existing therapies of WM.35 Additionally, multiple CXCR4 antagonists are reported to enhance the cytotoxic effect of rituximab or additional agents in diverse in vitro lymphoma models, including those of DLBCLs.19-23,36
Taken together, these data identify CXCR4 upregulation
as an indicator of sensitivity to proximal BCR/PI3K block- ade. These findings will potentially aid in the development of representative model systems and analyses of BCR/PI3K pathway-specific inhibitors. CXCR4 upregulation may also be an important and potentially targetable resistance mech- anism in BCR-dependent DLBCLs.
Funding
This work was supported by a ‘Mobility Plus’ fellowship from the Polish Ministry of Science and Higher Education (1261/MOB/IV/2015/0) (KB) and a Leukemia and Lymphoma Society SCOR award (MA. and SJR).
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