Intrachromosomal amplification 21: A driver of acute myeloid leukemia?

A 68-year-old woman was referred for anemia and circulating peripheral blood blasts. Bone marrow aspirate confirmed the diagnosis of acute myeloid leukemia (AML) with a background of variable dysplasia that was not otherwise sufficient to subclassify as AML with myelodysplasia-related changes (AML-MRC) (panel A; original magnification × 1000; Wright-Giemsa stain). By flow cytometry, the blasts were positive for dim/partial CD7, CD13, CD34, CD117, HLA-DR, partial MPO and TdT, and were negative for other B/T cell associated antigens. G-banding karyotype showed the presence of tandem duplication at the long arm of chromosome 21 (panel B; 46,XX,dup(21)(q21q22)). Single color fluorescence in situ hybridization probes targeting the 21q22.13-q22.2 region showed a homogeneously staining region on chromosome 21 containing >5 copies of RUNX1 (panels C and D; metaphase-interphase FISH), further confirmed by comparative genomic hybridization. Intrachromosomal amplification 21 (iamp21) is a well-recognized event in B lymphoblastic leukemia; however, it is rare in AML with <20 published cases, variably associated with morphologic dysplasia although it uniformly occurred in the setting of complex karyotypes. It was thus postulated to be a late event resulting from genome instability and chromothripsis. In our case, iAMP21 occurred as a sole abnormality, suggesting the possibility of a rather early role in leukemogenesis. N.A wrote the manuscript and compiled the genetics images. Z.C designed the cytology and flow cytometry images. Z.C revised the manuscript. The study received no funding from internal or external sources. The authors disclose no conflict of interests. The Institutional Review Board at the American University of Beirut exempted our single case report from review. Informed consent was explained to and signed by the patient. Data sharing is not applicable to this article as no new data were created or analyzed in this study.