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KIT mutations are recurrent genetic alterations in myeloid neoplasms (MNs), with the D816 hot-spot variant recognized as a poor prognostic marker in acute myeloid leukemia (AML) with RUNX1::RUNX1T1 and as a diagnostic criterion for systemic mastocytosis (SM). In contrast, the clinical and biological relevance of KIT mutations outside codon 816 remains insufficiently characterized. We retrospectively analyzed 40 MNs with pathogenic KIT mutations, comparing 26 cases harboring D816 variants to 14 cases with non-D816 changes. Clinicopathologic features, cytogenetics, molecular profiles, immunohistochemical data, and survival outcomes were evaluated. The two groups showed similar distributions of MN subtypes and cytogenetic abnormalities. However, the non-D816 group exhibited significantly lower mast-cell burden by CD117 immunohistochemistry and no cases of SM, whereas 31% of D816 cases showed concurrent or subsequent SM. D816 cases displayed more complex co-mutational profiles and a higher rate of KIT acquisition as a secondary event. Non-D816 cases demonstrated significantly longer overall survival. In the subset of AML with t(8;21), D816 variants trended toward inferior survival compared with non-D816 variants. Our findings suggest that non-D816 KIT mutations are associated with a less aggressive clinical phenotype, lower mast-cell differentiation, and improved outcomes. These results support a biologically distinct role of non-D816 KIT variants in MNs and highlight the need for refined risk stratification incorporating KIT variant classes.