Case Report: Acute myeloid leukemia with mixed immunophenotypic features and TCF3::ZNF384 fusion in a pediatric patient with CNS involvement: a diagnostic and therapeutic challenge.

Acute myeloid leukemia (AML) in the pediatric population can present significant diagnostic and therapeutic challenges, especially when immunophenotypic or genetic findings indicate mixed lineage features. Here, we present the case of an 11-year-old female patient who was initially diagnosed with AML (FLT3-ITD negative) and central nervous system (CNS-3) involvement. The leukemic blasts co-expressed myeloid markers (MPO, CD33, and CD13) as well as a low-intensity B-lymphoid antigen (CD19). Despite receiving two standard induction regimens (MEC and ADE), minimal residual disease (MRD) persisted. Next-generation sequencing (Illumina MiSeq; SOPHiA DDM Myeloid Plus) was performed on bone marrow aspirate collected after the second induction cycle (ADE), at which point MRD had become negative by flow cytometry but persistent MRD had been documented after the first induction (MEC). Post-induction NGS revealed a TCF3::ZNF384 fusion with a fusion read support of 75.04% (supported by 21,262 reads and 80.56% unique molecular coverage). This aberration is more commonly associated with B-ALL or mixed-phenotype acute leukemia (MPAL-B/M), which are both characterized by lineage plasticity and a higher risk of relapse. These results highlight the importance of comprehensive molecular testing and the need for therapeutic strategies that integrate both myeloid- and lymphoid-directed approaches, as well as meticulous MRD surveillance.