Epidermal Growth Factor Like -7 is a novel therapeutic target in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an aggressive, non-curative, mature B-cell lymphoma, with a median overall survival of 6-7 years. This underlines a need for effective therapeutic strategies to treat MCL better. Epidermal growth factor-like 7 (EGFL7) is a protein secreted by endothelial cells shown to play a critical role in angiogenesis. Our lab has previously demonstrated that EGFL7 supports the growth of leukemic blasts in AML patients; however, its role in MCL has not been investigated yet. In this study, we report EGFL7 mRNA is increased in MCL patient cells compared to healthy controls, and patients with high EGFL7 are associated with lower overall survival rates. Furthermore, EGFL7 is increased in plasma of MCL patients compared to plasma from healthy controls. We further show that EGFL7 binds to EGFR and activates AKT signaling pathway in MCL cells and that blocking EGFL7 in MCL: patient and cell lines decreases cell growth and increases apoptosis in vitro. Finally, anti-EGFL7 treatment inhibits tumor size and prolongs survival in a mouse model of MCL. In conclusion, our study reveals a role for EGFL7 in MCL cell proliferation and highlights EGFL7 inhibition as a promising new treatment for patients with MCL.