17. Intrachromosomal amplification of chromosome 21 as the sole chromosomal aberration in a primary AML patient

Intrachromosomal amplification of chromosome 21 (iAMP21), is a rare but recurrent acquired clonal chromosome aberration observed in acute myeloid leukemia (AML), usually associated with chemoresistance and poor prognosis. The vast majority of AML patients with iAMP21 also present with a complex karyotype and TP53 mutations, which are known markers for poor prognosis and interfere with understanding the clinical impact of iAMP21 in AML. We present a primary AML patient who had a bone marrow karyotype study showing additional material of unknown origin on 21q as the sole abnormality. The AML and high risk MDS FISH panel studies did not identify any abnormalities, including a normal signal pattern for RUNX1. Additional FISH studies for chromosome 21 detected five copies of the 21q22.13q22.2-specific signals on the derivative chromosome 21, suggestive of iAMP21. Chromosomal microarray analysis confirmed amplification of 21q, which included ERG and ETS2 genes but not RUNX1. The hematologic malignancy NGS panel revealed KIT and U2AF1 mutations. This 58-year-old male patient presented with pancytopenia and a hypercellular marrow with increased myeloblasts. This patient's disease was refractory to induction and salvage chemotherapy. While the clinical course showed similar chemoresistance as observed in other 21q-amplified AML, there is no concurrent TP53 aberration or complex karyotype observed in this case. This case demonstrates that iAMP21 may be an early driver for AML tumorigenesis, and these results implicate ERG and/or ETS2 instead of RUNX1 as the critical gene(s) of iAMP21 in AML. Further characterization of iAMP21 in AML and may provide opportunities for alternative therapies.