A new human mast cell line expressing a functional IgE receptor converts to tumorigenic growth by KIT D816V transfection - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Blood Année : 2014

A new human mast cell line expressing a functional IgE receptor converts to tumorigenic growth by KIT D816V transfection

Rosine Saleh
  • Fonction : Auteur
Ghaith Wedeh
  • Fonction : Auteur
Siham Bibi
  • Fonction : Auteur
Irina Sadovnik
  • Fonction : Auteur
Katharina Blatt
  • Fonction : Auteur
Emir Hadzijusufovic
  • Fonction : Auteur
Sylvie Jeanningros
  • Fonction : Auteur
Catherine Blanc
Magali Legarff-Tavernier
  • Fonction : Auteur
Elise Chapiro
Frédéric Subra
  • Fonction : Auteur
Patrick Bonnemye
  • Fonction : Auteur
Patrice Dubreuil
Vanessa Desplat
  • Fonction : Auteur
Michael Willmann
  • Fonction : Auteur
Thomas Ruelicke
  • Fonction : Auteur
Michel Arock
  • Fonction : Auteur

Résumé

In systemic mastocytosis (SM), clinical problems arise from factor-independent proliferation of mast cells (MCs) and the increased release of mediators by MCs, but no human cell line model for studying MC activation in the context of SM is available. We have created a stable stem cell factor (SCF)-dependent human MC line, ROSA(KIT WT), expressing a fully functional immunoglobulin E (IgE) receptor. Transfection with KIT D816V converted ROSA(KIT WT) cells into an SCF-independent clone, ROSA(KIT D816V), which produced a mastocytosis-like disease in NSG mice. Although several signaling pathways were activated, ROSA(KIT D816V) did not exhibit an increased, but did exhibit a decreased responsiveness to IgE-dependent stimuli. Moreover, NSG mice bearing ROSA(KIT D816V)-derived tumors did not show mediator-related symptoms, and KIT D816V-positive MCs obtained from patients with SM did not show increased IgE-dependent histamine release or CD63 upregulation. Our data show that KIT D816V is a disease-propagating oncoprotein, but it does not activate MCs to release proinflammatory mediators, which may explain why mediator-related symptoms in SM occur preferentially in the context of a coexisting allergy. ROSA(KIT D816V) may provide a valuable tool for studying the pathogenesis of mastocytosis and should facilitate the development of novel drugs for treating SM patients.

Dates et versions

hal-01514454 , version 1 (26-04-2017)

Identifiants

Citer

Rosine Saleh, Ghaith Wedeh, Harald Herrmann, Siham Bibi, Sabine Cerny-Reiterer, et al.. A new human mast cell line expressing a functional IgE receptor converts to tumorigenic growth by KIT D816V transfection. Blood, 2014, 124 (1), pp.111-120. ⟨10.1182/blood-2013-10-534685⟩. ⟨hal-01514454⟩
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