In summary, our observations together with previous data from the literature suggest that the efficacy of imatinib in terms of reducing MC tumor load in SM patients lacking the D816V KIT mutation, relies on the existence of imatinib-sensitive genetic defects such as extracellular membrane/transmembrane KIT mutations or PDGFR gene rearrangements, rather than on the absence of the KIT D816V mutation by itself. Here, KIT is linked to systemic mastocytosis.