AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation

Leukemia-specific AML1/ETO transcripts are detectable in most patients with t(8;21) acute myelogenous leukemia (AML) in long-term remission. To unders tand the inconsistency between the clinical cure and the presence of "resid ual disease" at a molecular level, we separated and identified the cells ex pressing AML1/ETO by phenotype and function. Here we demonstrate that AML1/ ETO transcripts are present in a fraction of stem cells, monocytes, and a c ells in remission marrow, and in a fraction of a cells in leukemic marrow, but not in T cells. AML1/ETO transcripts also were demonstrated in a fracti on of colony-forming cells of erythroid. granulocyte-macrophage, and/or meg akaryocyte lineages in both leukemic and remission marrow. These data stron gly suggest that the acquisition of the t(8;21) occurs at the level of stem cells capable of differentiating into B cells as well as all myeloid linea ges, and that a fraction of the AML1/ETO-expressing stem cells undergo addi tional oncogenic event(s) that ultimately leads to transformation into AML.