Although clinical trials with Midostaurin (PKC412) [41, 52] has yielded promising results, the existing discrepancy of TKIs toward KIT D816V mutations in vitro (effective) and in vivo (not effective) suggests the possibility of yet unknown additional co-operating mutations that may contribute to the development and pathogenesis of various subtypes of mastocytosis and influence the response to TKI therapy [42, 53, 54]. The gene discussed is KIT; the disease is mastocytosis.