title: Immunophenotypic profile predictive of KIT activating mutations in AML1-ETO leukemia.
abstract: 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 CD 19 and positive CD56 expression on leukemic blasts and, thus, can be phenotypically distinguished from AML1-ETO leukemias without KIT mutations.
authors: Department of Pathology and Laboratory Medicine, University of Texas Medical School, Houston.
authors: Jitakshi
authors: J
authors: De
authors: Reza
authors: R
authors: Zanjani
authors: Michele
authors: M
authors: Hibbard
authors: Bruce H
authors: BH
authors: Davis
mesh_terms: D001854:Bone Marrow Cells / Q000473:pathology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D003582:Cytogenetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D012189:Retrospective Studies
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D019009:Proto-Oncogene Proteins c-kit