Immunophenotypic profile predictive of KIT activating mutations in AML1-ETO leukemia

Translocation (8;21)/AML1-ETO is considered a favorable cytogenetic abnormality in acute myeloid leukemia (AML). However, associated KIT activating mutations confer poor outcome. The immunophenotype associated with KIT mutations in AML1-ETO has not previously been elucidated. We retrospectively reviewed the immunophenotype by flow cytometry of 56 cases of AML with t(8;21) and compared them with 100 cases of AML without t(8;21). In 21 t(8;21) cases, we sought KIT mutations by direct sequencing. Although CD19 and CD56 were aberrantly expressed in 42 (75%) of 56 and 46 (82%) of 56 cases, respectively, with t(8;21), these markers were only expressed in 4% and 25%, respectively, without t(8;21) (P < .001). However, the 5 KIT-mutated cases (D816H, 3; D816Y, 1; and N822K, 1) of t(8;21) AML had diminished CD19 expression (P = .04) with definite CD56 expression (P = .30) on myeloid blasts. Our study suggests that KIT activating mutations in AML with t(8;21) are associated with diminished CD19 and positive CD56 expression on leukemic blasts and, thus, can be phenotypically distinguished from AML1-ETO leukemias without KIT mutations.