Beside these promising preclinical findings in other tumor settings, the use of dual ETAR and ETBR antagonists could offer the advantage in CLL to target not only tumor cells (which express both receptors) but also surrounding EC, stromal cells and immune cells, which all expressed ETBR. Indeed, macitentan induces apoptosis in tumor-associated endothelial cells [10, 13, 37]. The gene discussed is EDNRB; the disease is B-cell chronic lymphocytic leukemia.