We tested this theory using two cell models comparing primary TK-sensitive mutations with secondary TK-insensitive mutations: The first model consists of a mast cell leukemia cell line (HMC1.1), which harbors an imatinib-sensitive KIT V560G mutation – and a derivative sister cell line (HMC1.2), which is characterized by a secondary activation loop KIT D816V mutation, rendering the cells insensitive towards imatinib [42,43]. This evidence concerns the gene KIT and mast cell leukemia.