A AML with a simultaneous false positive rearrangement: FISH interpretation pitfalls.

Introduction: rearrangement () is a common genomic alteration in acute leukemia that can be effectively targeted by menin inhibitors. While FISH is the standard laboratory test for , false positives can occur.

Case Report: We present a case of AML in which both and were identified by karyotype analysis and FISH. Although a targeted RNA next generation sequencing (NGS) assay confirmed the presence of the fusion, it did not detect a fusion transcript. To investigate the discrepancy between the positive FISH result and the negative fusion transcript, we performed whole-genome mate-pair DNA NGS to examine the locus on chromosome 11q23. This analysis revealed a breakpoint located 5.8 kb downstream of , which did not disrupt the gene itself. Given that FISH probes cover approximately 1 Mb around , this subtle shift led to a split-apart signal pattern mimicking a genuine rearrangement, resulting in a false positive FISH interpretation.

Conclusion: This case highlights a false positive in primary AML, indicating the need for additional molecular testing for confirmation.