Research Papers:

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

Siham Bibi _, Yanyan Zhang, Caroline Hugonin, Mallorie Depond Mangean, Liang He, Ghaith Wedeh, Jean-Marie Launay, Sjoerd Van Rijn, Thomas Würdinger, Fawzia Louache and Michel Arock

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Oncotarget. 2016; 7:82985-83000. https://doi.org/10.18632/oncotarget.12824

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Siham Bibi1, Yanyan Zhang2, Caroline Hugonin1, Mallorie Depond Mangean2, Liang He2, Ghaith Wedeh1, Jean-Marie Launay3, Sjoerd Van Rijn4, Thomas Würdinger4,5, Fawzia Louache2, Michel Arock1,6

1Molecular and Cellular Oncology Research Group, LBPA CNRS UMR 8113, Ecole Normale Supérieure de Cachan, Cachan, France

2INSERM Unit U1170, Hématopoïèse normale et pathologique, Gustave Roussy Campus, Université Paris Sud Villejuif, France

3Laboratoire de Biochimie et Biologie Moléculaire, Inserm U942, Hôpital Lariboisière, AP-HP, Université Paris Diderot - Paris VII Paris, France

4Neuro-oncology Research Group, Department of Neurosurgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherland

5Neuroscience Center, Department of Neurology, Massachussetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA, USA

6Laboratoire Central d’Hématologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Université Pierre et Marie Curie (UPMC) Paris VI, Paris, France

Correspondence to:

Siham Bibi, email: [email protected]/[email protected]

Keywords: KIT D816V mutant, ROSAKIT D816V cell line, gluc reporter, NSG mice, advanced systemic mastocytosis

Received: August 08, 2016     Accepted: October 12, 2016     Published: October 22, 2016


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 γ-/- mice, using Gaussia princeps luciferase as a reporter. Intravenous injection of ROSAKIT 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 ROSAKIT 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.

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