Rapid Molecular Diagnostics Enables Individualized Frontline Treatment of CBFA2T3::GLIS2 ‐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