Novel NUTM1 Fusions in Relapsed Acute Myeloid Leukemia: Expanding the Genetic and Clinical Landscape

Gene fusions involving <i>NUTM1</i> have been increasingly recognized in hematologic malignancies, though their role in acute myeloid leukemia (AML) remains poorly understood. We retrospectively analyzed 565 unique AML patients with reported fusion results who underwent comprehensive next-generation sequencing (NGS) between March 2022 and December 2023. Among them, three novel in-frame <i>NUTM1</i> fusion transcripts, <i>LARP1::NUTM1</i>, <i>ARHGAP15::NUTM1,</i> and <i>GABPB1::NUTM1</i>, were identified in three relapsed or refractory AML cases, all with monocytic differentiation. Ancillary studies included flow cytometry, cytogenetics, FISH, and comprehensive mutational profiling. All three patients eventually relapsed and succumbed to their disease, despite initial responses in one case. Each case also harbored co-occurring mutations associated with adverse prognosis, such as <i>BCOR, ASXL1,</i> and <i>RUNX1</i>. These findings suggest <i>NUTM1</i> fusions in AML could represent a distinct molecular subset with potentially poor prognosis, warranting further functional and clinical investigation to clarify their biological and therapeutic significance.