Clinical Information

Acquired mutations in the KIT gene are identified in a subset of acute myeloid leukemias (AML) characterized by inv16 or t(16;16) CBFB-MYH11 or t(8;21) RUNX1-RUNX1T1 genetic abnormalities (approximately 10%-20% of cases) and in this setting, the additional presence of KIT gene mutation has been described as an adverse prognostic factor in some studies. KIT mutations in AML tend to involve exons 8 through 11 and 17, although the p.Asp816Val (D816V) variant that is highly prevalent in systemic mastocytosis is less common in AML. Mastocytosis is a hematologic disorder characterized by abnormal mast cell expansion in the bone marrow and extramedullary organ sites (eg, skin, gastrointestinal tract). Disease can be localized to skin (ie, cutaneous mastocytosis) or present systemically, with variable features of disease aggressiveness and symptomatology. Mutations in the KIT gene are identified in a large majority of patients with both cutaneous mastocytosis (CM) and systemic mastocytosis (SM). The D816V abnormality is identified in most patients with SM and this finding represents an important minor diagnostic criterion in the 2008 WHO classification. The D816V is less commonly seen in CM, although single nucleotide variants are present in other KIT exons. Rare cases of familial mastocytosis are also described with KIT mutations involving exons 8 and 9. Although KIT gene mutation represents an important diagnostic marker for SM, the number of bone marrow mast cells is often limited in aspirate samples. Therefore, if SM is clinically and pathologically suspected, KIT testing should first proceed with a sensitive and specific screen for the D816V (KITB / KIT Asp816Val Mutation Analysis, Blood; KITBM / KIT Asp816Val Mutation Analysis, Qualitative PCR, Bone Marrow; or KITAS / KIT Asp816Val Mutation Analysis, Qualitative PCR) prior to consideration of KIT gene sequencing, based on the greatly enhanced sensitivity of the PCR test for this particular variant. In AML, KIT sequencing is preferred, given the wider spectrum of mutations in other KIT exons.