Insights into the biological features and improved diagnostics of adult acute myeloid leukemia via fusion genes identified through targeted next-generation sequencing.

BACKGROUND

Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia (AML). This study investigated the utility of targeted next-generation sequencing (NGS) of RNA for detecting rare and unknown fusion genes in patients with AML.

METHODS

A total of 85 adult AML samples previously identified as fusion gene-negative by multiplex nested reverse transcription-polymerase chain reaction (RT-PCR) were subjected to NGS analysis.

RESULTS

Fusion genes were detected in 21 of 72 (29.2%) patients. Among the 26 primary refractory patients, 11 (42.3%) exhibited fusion genes, whereas among the 18 relapsed patients, fusion genes were identified in five (27.8%). Notably, KMT2A and NUP98 rearrangements were enriched in refractory/relapsed patients. Additionally, recurrent fusion transcripts involving EIF4A1 were observed. The identification of additional fusion genes resulted in an approximate 20.8% (11/53) reclassification of medium-risk karyotypes to the high-risk category, thereby enhancing diagnostic accuracy.

CONCLUSIONS

Targeted NGS may complement conventional methods for identifying novel fusions in refractory/relapsed AML; however, its prognostic utility requires verification in controlled trials.