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

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, patients with CBF AML were therefore analyzed for the KIT D816V mutation and mutation positive cases subsequently analyzed for the presence of SM. The KIT D816V mutation was detected in eight 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 eight mutation positive patients, with levels ranging from 0.04 to 98% in a pretreatment blood sample. Five of the eight 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 eight KIT D816V mutation positive cases fulfilled the World Health Organization 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.