Optical genome mapping reveals a recurrent translocation, t(14;16), in T/myeloid mixed phenotype acute leukemia: report of two cases.

backgroundT/myeloid mixed-phenotype acute leukemias (MPAL-T/M) is a type of rare and high-risk acute leukemia that carries both T- and myeloid- lineage markers. The diagnosis of MPAL requires integration of clinical, immunophenotypic, and genetic information. Optical Genome Mapping (OGM) technology is a particularly powerful tool to profile genome-wide variants and locate complex chromosomal rearrangements that may guide diagnosis and risk stratification in MPAL-T/M. CASE PRESENTATION: We report two MPAL-T/M cases with comprehensive clinical, immunophenotype, and genetic results. A shared chromosomal rearrangement between chromosomes 14q32 and 16q24, t(14;16)(q32;q24), was detected in both leukemias. The t(14;16) has breakpoints 500-900 kb downstream to the BCL11B gene on chromosome 14, and within or near LINC01081 on chromosome 16, juxtaposing BCL11B enhancer to a novel gene on chromosome 16. In addition, both leukemias were positive for WT1 mutations and negative for FLT3-ITD.

conclusionThese cases represent the first report of recurrent translocation, t(14;16), in MPAL-T/M. The t(14;16) with these breakpoints is consistent with the juxtaposition of BCL11B enhancer to a novel gene on chromosome 16, similar to BCL11B::TLX3 in T-ALL. This report highlights the clinical relevance of OGM in identifying critical gene rearrangement that creates enhancer hijacking in the diagnosis of MPAL-T/M. These discoveries, along with further chromatin topology and gene expression studies, may provide a new window into the underlying biology of these aggressive leukemias.