Systemic mastocytosis uncommon in KIT D816V mutation positive core-binding factor acute myeloid leukemia

Abstract The KIT D816V mutation is detected in the vast majority of adult cases of systemic mastocytosis (SM). The mutation is also frequently detected in core-binding factor acute myeloid leukemia (CBF-AML) defined by the presence of t(8;21)(q22;q22); RUNX1-RUNX1T1 or inv(16)(p13.1;q22)/t(16;16)(p13.1;q22); CBFB-MYH11 chromosomal rearrangements, but whether the mutation is indicative of associated SM is unclear. In the present study, CBF-AML patients were therefore analysed for the KIT D816V mutation and mutation positive cases subsequently analysed for the presence of SM. The KIT D816V mutation was detected in 8 of 20 cases of CBF-AML with the frequency in t(8;21)(q22;q22) and inv(16)(p13.1;q22) positive cases being 31% and 57%, respectively. The fraction of KIT D816V mutation positive cells was highly variable among the 8 mutation positive patients with levels ranging from 0.04 - 98% in a pre-treatment blood sample. Five of the 8 cases carried the mutation in a cell fraction below one-tenth of the blast cell fraction, thus suggesting that KIT mutation is often a late event in leukemogenesis. None of the 8 KIT D816V mutation positive cases fulfilled the WHO diagnostic criteria of SM. The presence of the KIT D816V mutation in the CBF-AML subgroup can therefore not be considered indicative of associated SM.