Complex chromosome rearrangement t(8;21)(p21;q22.1)inv(8)(p21q22.1), a novel variant of t(8;21) in acute myeloid leukemia. J. Xu¹, L. Mak¹, C. Richmond¹, R.C. Lohmann². 1) Cytogenetics; 2) Hematology, London Health Sciences Centre and University of Western Ontario, Canada.
   We report a novel variant of 8;21 translocation in acute myeloid leukemia and propose cytogenetics mechanisms for this rearrangement. This is a case study by routine karyotyping and FISH using ETO (8q22)/AML1 (21q22) dual color, dual fusion translocation probe set (Vysis). A 72-year-old female patient was diagnosed with AML and 95% of her bone marrow cells were blast cells, confirmed myeloblasts on flow cytometry. Routine cytogenetics of the bone marrow cells showed a complex karyotype with 8;21 translocation and an inversion involving the translocated chromosome 8. The detailed karyotype is 46,XX,der(8)(21qter->21q22.1::8q22.1->8p21::8q22.1->8qter),der(21)(21pter->21q22.1::8p21->8pter[24]/46,XX[1]. FISH showed that the der(8p) had yellow ETO/AML1 fusion signal whereas the der(21q) had green AML1 signal but no ETO/AML1 fusion signal. We propose that this complex karyotype is possibly a result of 3 rearrangements: inversion, translocation and deletion. It might begin with a pericentric inversion of 8p21q22.1 with the breakpoint being distal to ETO at 8q22. This inversion would have relocated the entire ETO to the der(8p), as was evidenced by absence of orange ETO signal in the der(8q). This might be followed by 8p;21q translocation, as was evidenced by the presence of the ETO/AML1 fusion signal in the der(8p). There was deletion of ETO in der(21), as was indicated by no fusion/orange signals in the chromosome. This is a new variant to a list of reported cytogenetics variants of the classical t(8;21) involving various chromosome partners identified by routine karyotyping and submicroscopic variants of ETO/AML1 detected by FISH or RT-PCR. More case reports and further cytogenomics studies will help understand clinical and prognostic significance of such variants. Our finding emphasizes that caution be exercised in interpretation of variant ETO/AML1 signal patterns in interphase and metaphase FISH.