# TRAF3IP3::FGFR1: a novel FGFR1 fusion identified in an aggressive case of acute myeloid leukemia

## TL;DR

A new FGFR1 gene fusion was found in a deadly case of acute myeloid leukemia, suggesting possible new treatment options.

## Contribution

The discovery of a novel TRAF3IP3::FGFR1 fusion in acute myeloid leukemia expands the known FGFR1-rearranged neoplasms.

## Key findings

- A novel TRAF3IP3::FGFR1 fusion was identified in a patient with aggressive acute myeloid leukemia.
- The fusion retained key functional domains, suggesting oncogenic potential and signaling capability.
- The case highlights the importance of genomic profiling for aggressive leukemias and potential for FGFR1-targeted therapies.

## Abstract

Myeloid/lymphoid neoplasms with tyrosine kinase gene fusions (MLN-TK) are rare hematologic malignancies characterized by recurrent kinase rearrangements, including FGFR1, often associated with aggressive clinical behavior. We report the first case of acute myeloid leukemia (AML) harboring a novel TRAF3IP3::FGFR1 fusion, identified by whole transcriptome sequencing. The patient, a 35-year-old man, presented with monocytic AML and succumbed to disease within 40 days despite induction chemotherapy. Cytogenetic and molecular profiling revealed a complex monosomal karyotype and a pathogenic TP53 mutation, both known adverse prognostic markers. The in-frame fusion retained the coiled-coil domain of TRAF3IP3 and the full tyrosine kinase domain of FGFR1, suggesting preserved dimerization and oncogenic signaling. This case broadens the spectrum of FGFR1-rearranged neoplasms and highlights the importance of early genomic profiling in aggressive leukemia. It also underscores the potential therapeutic opportunities with FGFR1-targeted agents such as pemigatinib.