Targeting of CXCR4 by the Naturally Occurring CXCR4 Antagonist EPI-X4 in Waldenström’s Macroglobulinemia

摘要

Waldenström’s Macroglobulinemia is a B-cell lymphoma, for which no curative established treatment exists. One of the drivers of tumor growth in this disease are genetic alterations of the gene CXCR4, which can be found in up to 40% of patients with this disease. Patients with CXCR4 mutations typically have a more aggressive disease. In this article we provide evidence that a naturally occurring peptide, called EPIX4 and its optimized derivatives bind to CXCR4 on Waldenström’s macroglobulinemia cells and are able to impair growth of these lymphoma cells in mice. These data highlight that there are natural mechanisms which counteract CXCR4 driven lymphoma growth. In addition, they underline that optimizing naturally occurring CXCR4 antagonists can potentially lead to the development of novel therapies in Waldenström’s macroglobulinemia, particular in patients with CXCR4 alterations affected by a more aggressive course of disease.