De Jitakshi, Zanjani Reza, Hibbard Michele, Davis Bruce H
Department of Pathology and Laboratory Medicine, University of Texas Medical School, Houston.
Am J Clin Pathol. 2007 Oct;128(4):550-7. doi: 10.1309/JVALJNL4ELQMD536.
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.
在急性髓系白血病（AML）中，易位（8；21）/AML1-ETO被认为是一种预后良好的细胞遗传学异常。然而，与之相关的KIT激活突变会导致预后不良。此前尚未阐明AML1-ETO中与KIT突变相关的免疫表型。我们回顾性地通过流式细胞术分析了56例t（8；21）AML的免疫表型，并将其与100例无t（8；21）的AML病例进行比较。在21例t（8；21）病例中，我们通过直接测序寻找KIT突变。虽然在56例t（8；21）病例中，分别有42例（75%）和46例（82%）异常表达CD19和CD56，但在无t（8；21）的病例中，这些标志物的表达率仅分别为4%和25%（P <.001）。然而，5例t（8；21）AML的KIT突变病例（D816H，3例；D816Y，1例；N822K，1例）的髓系原始细胞CD19表达降低（P =.04），CD56呈明确表达（P =.30）。我们的研究表明，t（8；21）AML中的KIT激活突变与白血病原始细胞CD19表达降低和CD56阳性表达相关，因此在表型上可与无KIT突变的AML1-ETO白血病相区分。
