A Rare Case of De Novo Acute Myeloid Leukemia, Featuring a KMT2A (MLL) Amplification

We present a case of a patient in their 80s initially presenting with myelodysplastic syndromes (MDS). Chromosomal analysis showed an abnormal female karyotype with a complex karyotype. Metaphase FISH confirmed four copies of <i>KMT2A (MLL)</i> in 24.5% [49/200] and amplification of <i>KMT2A</i> (<i>MLL</i>) with more than four copies in 22% [44/200]. FISH also revealed the presence of <i>MYC</i> (8q24) on the long arm of chromosome 2 at 2q33 locus, two copies of <i>BCR</i> on each homolog 22, and two additional copies of <i>BCR</i> on a derivative chromosome 22. Flow cytometric analysis revealed a population of aberrant myeloid blasts (15-17%). Bone marrow analysis showed hypercellular marrow with a significant increase in myeloid blasts (~50%) and trilineage dysplasia. Eventually, these findings were consistent with a final diagnosis of acute myeloid leukemia non-M3 and a complex karyotype, correlating with cytogenetics, flow cytometry, molecular, and clinical findings. The patient's clinical course was marked by a rapid deterioration, including recurrent arrhythmias, hypoxic respiratory failure, and septic shock. Given their poor clinical status and adverse-risk molecular profile, care was transported to hospice. The presence of <i>KMT2A</i> amplification is a rare event in AML and is present in ~1% of AML and MDS cases. <i>MYC</i> translocation, <i>KMT2A</i> (<i>MLL</i>) amplification, and 5q/20q losses suggest secondary therapy-related AML and categorize this case in the adverse risk prognosis under the ELN 2022 guidelines.