Acute Myeloid Leukaemia Driven by Rare HNRNPH1::ERG Fusion Gene in an Adult, With Distinct Transcripts Detected by...

Acute myeloid leukaemia (AML) cases with rare fusion genes, such as ERG-related fusions, constitute less than 1% of AML. They often present with a normal karyotype by conventional cytogenetics but are increasingly detected by RNA sequencing (RNAseq), although their characteristics and the utility of fusion genes as an MRD marker are poorly defined. We report a case of a 19-year-old female presenting with HNRNPH1::ERG AML, the fifth reported case to our knowledge, who developed a second HNRNPH1::ERG fusion at relapse that was not detectable on the original MRD assay. This case highlights potential mechanisms driving disease recurrence and underscores the importance of characterizing MRD kinetics and transcript dynamics to inform prognosis and therapeutic decisions. We highlight the benefit of incorporating RNAseq into testing both at diagnosis and at relapse, and the need to further characterise MRD kinetics for rare fusion genes in AML.

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