# Rapid Development of Unclassified Myeloid Lineage Acute Leukaemia With Trisomy 6 and U2AF1 Mutation

## TL;DR

A rare case of unclassified myeloid leukemia with unusual genetic features and aggressive progression is reported, highlighting diagnostic challenges.

## Contribution

The case presents a novel leukemia subtype with trisomy 6 and U2AF1 mutation that defies current classification systems.

## Key findings

- The leukemia exhibited atypical myeloid cells with extramedullary tumor formation and trisomy 6.
- Clonal evolution led to a new leukaemic cell clone with monocytoid differentiation and additional mutations.
- The disease progressed despite standard therapy, leading to fatal complications.

## Abstract

We present a case of acute clonal bone marrow 98% infiltration of atypical myeloid cells with borderline hypogranular/agranular promyelocytes/myelocytes and occasional blast cells maturity, which also formed extramedullary tumours in the chest wall, with isolated trisomy of chromosome 6 and pathogenic variant U2AF1 (S34F) that escapes established acute myeloid leukaemia (AML) diagnostic criteria according to the World Health Organization (WHO) classification. Following standard daunorubicin and cytarabine induction therapy, the disease progressed with the appearance of a previously undetected clone of leukaemic cells with a distinct immunophenotype demonstrating monocytoid differentiation and clonal evolution to a hypo‐tetraploid karyotype with an average number of 84 chromosomes and new pathogenic NRAS and ZRSR2 mutations. The patient reactivated refractory disseminated intravascular coagulation (DIC) leading to a progressive supratentorial hematoma and finally cardiac arrest. In conclusion, our report shows that atypical clonal myelocytes can massively infiltrate the bone marrow and form extramedullary tumours, justifying the diagnosis and treatment of acute leukaemia, although they did not fit the current classification.