Preclinical human models and emerging therapeutics for advanced systemic mastocytosis.

Mastocytosis is a term used to denote a group of rare diseases characterized by an abnormal accumulation of neoplastic mast cells in various tissues and organs. In most patients with systemic mastocytosis, the neoplastic cells carry activating mutations in Progress in mastocytosis research has long been hindered by the lack of suitable models, such as permanent human mast cell lines. In fact, only a few human mast cell lines are available to date: HMC-1, LAD1/2, LUVA, ROSA and MCPV-1. The HMC-1 and LAD1/2 cell lines were derived from patients with mast cell leukemia. By contrast, the more recently established LUVA, ROSA and MCPV-1 cell lines were derived from CD34 cells of non-mastocytosis donors. While some of these cell lines (LAD1/2, LUVA, ROSA and MCPV-1) do not harbor mutations, HMC-1 and ROSA cells exhibit activating mutations found in mastocytosis and have thus been used to study disease pathogenesis. In addition, these cell lines are increasingly employed to validate new therapeutic targets and to screen for effects of new targeted drugs. Recently, the ROSA subclone has been successfully used to generate a unique model of advanced mastocytosis by injection into immunocompromised mice. Such a model may allow validation of data obtained with targeted drugs directed against mastocytosis. In this review, we discuss the major characteristics of all available human mast cell lines, with particular emphasis on the use of HMC-1 and ROSA cells in preclinical therapeutic research in mastocytosis.