A novel IKZF1::FAM3C fusion associated with inversion of chromosome 7, inv(7)(p13q32), in relapsed acute myeloid leukemia.

BACKGROUND

Acute myeloid leukemia (AML) is characterized by myeloid blasts in the bone marrow and peripheral blood, and it is a highly heterogenous disease genetically. Although our understanding of AML genetics has advanced considerably, disease relapse continues to pose a significant therapeutic hurdle.

CASE PRESENTATION: Here, we report a case of relapsed AML following allogeneic stem cell transplantation (alloSCT) with a novel in-frame IKZF1::FAM3C fusion detected by RNA sequencing. Karyotype analysis revealed a pericentric inversion of chromosome 7, inv(7)(p13q32), which is the likely mechanism for this fusion. While IKZF1 deletions are a common feature in B-cell acute lymphoblastic leukemia (B-ALL) and are linked to poor outcomes, especially in children, they are rarely reported in AML. To our knowledge, gene fusions involving IKZF1 have not been previously described in AML, although deletion of the short arm of chromosome 7 involving the IKZF1 gene is relatively common.

CONCLUSIONS

This case broadens the spectrum of IKZF1 rearrangements in hematologic malignancies and suggests a potential role for disrupted Ikaros function in AML pathogenesis.