Rapid Molecular Diagnostics Enables Individualized Frontline Treatment of <i>CBFA2T3::GLIS2</i> ‐Rearranged Acute Myeloid Leukemia

In this paper, we discuss how Nanopore whole genome sequencing (WGS) was utilized for rapid genomic identification of CBFA2T3::GLIS2-rearranged acute myeloid leukemia (AML) for two pediatric patients. Patients with CBFA2T3::GLIS2 AML have a 27% 5-year event-free survival. Prior case reports demonstrated that recurrent CBFA2T3::GLIS2 AML has a favorable treatment response to azacitidine, venetoclax, and gemtuzumab. Nanopore WGS enabled early recognition of the CBFA2T3::GLIS2 rearrangement, providing the opportunity to choose alternative therapies upfront with azacitidine, venetoclax, and gemtuzumab. We discuss our patients' status and the implications of a rapid molecular diagnostic method like Nanopore WGS. Trial Registration: Clinicaltrials.gov identifier: NCT06609928.