Optical genome mapping (Bionano – Saphyr) for AML associated with cryptic chromosomal recurrent abnormality

Here, we report the diagnostic work-up of a thirty-three-year-old woman presenting with 77% bone marrow myeloid blasts. Conventional cytogenetic did not show any recurrent abnormality but four mutations were found in three genes: FLT3, CEBPA and IDH1. This AML was considered “AML with CEBPA mutation” (2022 WHO classification) with an intermediate prognosis according to the 2022 ELN recommendations. On top of that, the newly described Optical Genome Mapping (OGM) technology was used to search for a potential structural variant. Using this assay, we detected a NUP98::NSD1 fusion in the bone marrow cells. This infrequent but recurrent translocation was subsequently confirmed by specific FISH and RNA-sequencing (Archer®). It is associated with high induction failure and poor survival in AML. In summary, the OGM approach can efficiently detect cryptic chromosomal aberrations in AML, which could change the prognosis and guide the patient’s treatment.