Optical Genome Mapping Reveals Complex and Cryptic Rearrangement Involving :: Fusion in Acute Promyelocytic Leukemia.

Acute promyelocytic leukemia (APL) is an aggressive subtype of acute myeloid leukemia (AML), characterized by the hallmark translocation t(15;17) resulting in a :: fusion. Once diagnosed, APL is now considered to be one of the most treatable forms of AML. However, without early detection and treatment, the disease is associated with rapid deterioration and lethal side effects. We describe a case of diagnostic APL presenting with a normal karyotype, normal break-apart FISH, and unclear, atypical FISH findings. We used optical genome mapping (OGM) to characterize this atypical fusion. OGM allowed for detection of a :: fusion resulting from a cryptic and complex insertion of into on 17q21.2 whereby a segment of 15q24.1 was inserted into the 17q21.2. The recipient breakpoint of the insertion was at intron 2 of the gene and the donor breakpoint of the insertion was at exon 5/intron 6 of the gene. This is the first report of an insertional :: fusion into the gene on 17q detected by OGM. OGM has demonstrated its utility in a clinical cytogenetics environment, allowing for clearer characterization and diagnosis of various neoplasms.