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

TL;DR

An elderly patient with a rare form of acute myeloid leukemia showed KMT2A amplification and complex genetic changes, leading to a poor prognosis.

Contribution

This paper reports a rare case of KMT2A amplification in AML, highlighting its association with adverse prognosis and complex cytogenetics.

Findings

KMT2A (MLL) amplification was detected in 46.5% of cells, with four or more copies in 22%.

The patient's leukemia was associated with a complex karyotype and adverse-risk molecular features.

Clinical outcomes were poor, leading to hospice care due to rapid deterioration and high-risk profile.

Abstract

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 KMT2A (MLL) in 24.5% [49/200] and amplification of KMT2A (MLL) with more than four copies in 22% [44/200]. FISH also revealed the presence of MYC (8q24) on the long arm of chromosome 2 at 2q33 locus, two copies of BCR on each homolog 22, and two additional copies of BCR 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 KMT2A amplification is a rare event in AML and is present in ~1% of AML and MDS cases. MYC translocation, KMT2A (MLL) amplification, and 5q/20q losses suggest secondary therapy-related AML and categorize this case in the adverse risk prognosis under the ELN 2022 guidelines.

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