Systemic mastocytosis (SM) are rare and still non curable diseases characterized by the proliferation of neoplastic mast cells (MC) in the bone marrow and other organs/tissues such as the skin, the gastro-intestinal tract and the spleen, whose physiopathology relies on the presence of the KIT D816V activating mutation (and in advanced forms of additional genetic defects) in the neoplastic MC. The severity of the disease varies from patient to patient. The advanced forms of SM (AdvSM) have a poor prognosis and are poorly sensitive to tyrosine kinase inhibitors (TKIs) targeting KIT (midostaurin). This resistance might be explained by the fact that, in AdvSM, the MC present additional mutations in TET2, ASXL1, RUNX1, SF3B1 and/or SRSF2. Thus, in order to find new therapeutic combinations able to overcome this resistance, we work on a human MC line presenting with the KIT D816V mutation and a mutation of SF3B1 (K700E), in which we study the expression of anti-apoptotic molecules. Indeed, we believe that the concomitant presence of the KIT D816V mutation and of other mutations induces overexpression of Bcl-2 and Mcl-1, accounting for the resistance to TKIs. Given this hypothesis, we test combinations of midostaurin and compounds targeting Bcl-2 or Mcl-1, in order to assess a potential synergistic antiproliferative and pro-apoptotic effect on neoplastic MC.