We find that neoplastic human MCs with oncogenic KIT mutations (including HMC-1.2 and bone marrow CD25+ malignant MC from patients with SM) as well as other cells carrying D816V-KIT, are more vulnerable to inhibition of SPHK1 than normal MCs or other cell counterparts lacking this mutation. The gene discussed is SPHK1; the disease is systemic mastocytosis.