A new humanized in vivo model of KIT D816V(+) advanced systemic mastocytosis monitored using a secreted luciferase

作者：Bibi Siham; Zhang Yanyan; Hugonin Caroline; Mangean Mallorie Depond; He Liang; Wedeh Ghaith; Launay Jean Marie; Van Rijn Sjoerd; Wurdinger Thomas; Louache Fawzia; Arock Michel

来源：Oncotarget, 2016, 7(50): 82985-83000.

DOI：10.18632/oncotarget.12824

• KIT D816V mutant
• ROSA(KIT D816V) cell line
• gluc reporter
• NSG mice
• advanced systemic mastocytosis

Systemic mastocytosis are rare neoplasms characterized by accumulation of mast cells in at least one internal organ. The majority of systemic mastocytosis patients carry KIT D816V mutation, which activates constitutively the KIT receptor. Patient with advanced forms of systemic mastocytosis, such as aggressive systemic mastocytosis or mast cell leukemia, are poorly treated to date. Unfortunately, the lack of in vivo models reflecting KIT D816V+ advanced disease hampers pathophysiological studies and preclinical development of new therapies for such patients. Here, we describe a new in vivo model of KIT D816V(+) advanced systemic mastocytosis developed by transplantation of the human ROSAKIT D816V-Gluc mast cell line in NOD-SCID IL-2R g(-/-) mice, using Gaussia princeps luciferase as a reporter. Intravenous injection of ROSA(KIT D816V-Gluc) cells led, in 4 weeks, to engraftment in all injected primary recipient mice. Engrafted cells were found at high levels in bone marrow, and at lower levels in spleen, liver and peripheral blood. Disease progression was easily monitored by repeated quantification of Gaussia princeps luciferase activity in peripheral blood. This quantification evidenced a linear relationship between the number of cells injected and the neoplastic mast cell burden in mice. Interestingly, the secondary transplantation of ROSA(KIT D816V-Gluc) cells increased their engraftment capability. To conclude, this new in vivo model mimics at the best the features of human KIT D816V(+) advanced systemic mastocytosis. In addition, it is a unique and convenient tool to study the kinetics of the disease and the potential in vivo activity of new drugs targeting neoplastic mast cells.

• 出版日期2016-12-13