Persistence of AML1 rearrangement in peripheral blood cells in t(8;21)

Translocation (8;21)(q22;q22) involves fusion of the AML1 gene with the ETO gene, generating an AML1/ETO fusion transcript that can be detected by the polymerase chain reaction (PCR). Persistence of the AML1/ETO transcript has been demonstrated by PCR in patients with t(8;21) in long-term remission, but the rearranged AML1 gene could not be detected by Southern analysis, showing that the t(8;21) clone existed as minimal residual disease (MRD). In one patient with t(8;21), AML1/ETO could be detected serially in the peripheral blood. However, rearrangement of the AML1 gene was also found to persist. Furthermore, the hybridization intensities of the rearrangement bands showed that some of the mature myeloid cells also possessed the AML1 rearrangement. Thus, the presence of AML1/ETO in this case appeared to be due to persistence of the mutated clone as mature myeloid cells instead of MRD, implying that the t(8;21) had occurred in a preleukemic myeloid progenitor cell capable of differentiation.