Thrombopoietin Inhibits Murine Mast Cell Differentiation

¹ Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome
² Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome; Departments of Biomorphology, University of Chieti, Chieti, Italy
³ Departments of Quality and Safety of Animal Experimentation, Istituto Superiore Sanità, Rome
⁴ Departments of Hematology, University of Florence, Florence
⁵ Departments of Biomorphology, University of Chieti, Chieti, Italy
⁶ Departments of Kirin Brewery Pharmaceutical Research Laboratory, Gunma, Japan
⁷ Departments of Medicine, Mont Sinai School of Medicine, New York, NY, USA
⁸ Departments of Cell Biology and Neurosciences, Istituto Superiore Sanità, Rome
⁹ Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome; Departments of Medicine, Mont Sinai School of Medicine, New York, NY, USA and Myeloproliferative Disease– Research Consortium (MPD-RC)

^* To whom correspondence should be addressed. E-mail: annarita.migliaccio{at}mssm.edu.

	Abstract

We have recently shown that Mpl, the thrombopoietin receptor, is expressed on murine mast cells and on their precursors and that targeted deletion of the Mpl gene increases mast cell differentiation in mice. Here we report that treatment of mice with thrombopoietin, or addition of this growth factor to bone marrow-derived mast cell cultures, severely hampers the generation of mature cells from their precursors by inducing apoptosis. Analysis of the expression profiling of mast cells obtained in the presence of thrombopoietin suggests that thrombopoietin induces apoptosis of mast cells by reducing expression of the transcription factor Mitf and its target anti-apoptotic gene Bcl2.