Human Lymphatic Endothelial Cells Expressing NRAS^Q61R Model Characteristics of Kaposiform Lymphangiomatosis

Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly characterized by lymphatic overgrowth and dysfunction. The goal of this study was to determine how the NRAS^Q61R variant found in the tissue of KLA patients impacts key characteristics of lymphatic endothelial cells (LEC). LEC expressing NRAS^Q61R had a spindled morphology, increased migration, increased proliferation, increased MAPK signaling, and elevated angiopoietin-2 production. In an in vitro lymphangiogenesis model, LEC expressing NRAS^Q61R showed increased sprouting and formed enlarged and disorganized vascular structures. This model of LEC expressing NRAS^Q61R can be used to give insights into KLA pathogenesis and test new treatments.