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.

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.

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