The t(8;21) translocation, which generates a chimeric gene, AML1/ETO, is one of the most common chromosomal abnormalities in acute myeloid leukemia (AML) and is associated with a good clinical outcome. However, the clinical features of t(8;21)AML with additional genetic aberrations have not been well elucidated. In this study, we screened for KIT mutations in 44 patients with t(8;21)AML. While 2 cases had a silent type mutation at codon 546 in the juxtamembrane domain, Lyn546Lyn, 8 cases (17.8%) had Asp816 mutations in the tyrosine kinase domain, Asp>Asn in 2 cases, Asp>Tyr in 4 cases, Asp>Val in 1 case and Asp>His in 1 case. Patients with Asp816 mutations showed leukocytosis (P = 0.001) and poor overall survival (P < 0.0001), when compared to those without Asp816 mutations. When the Asp816 mutation was transfected into a stem cell factor-dependent cell line, Mo7e, the cells grew rapidly and displayed stem cell factor-independent proliferation. These results suggest that t(8;21)AML with Asp816 mutations in KIT may be a distinctive subtype of t(8;21)AML and that this genetic aberration has an adverse effect on the clinical outcome for t(8;21)AML.

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