Utilization of RT-PCR and Optical Genome Mapping in Acute Promyelocytic Leukemia with Cryptic PML::RARA Rearrangement: A Case Discussion and Systemic Literature Review

Acute promyelocytic leukemia (APL) is characterized by abnormal promyelocytes and t(15;17)(q24;q21) PML::RARA. Rarely, patients may have cryptic or variant rearrangements. All-trans retinoic acid (ATRA)/arsenic trioxide (ATO) is largely curative provided that the diagnosis is established early. We present a case in which the diagnostic work-up suggested a diagnosis of APL; however, FISH, using the PML/RARA dual fusion and RARA breakapart probes, was negative. RT-PCR later revealed a cryptic fusion transcript. Optical genome mapping (OGM) confirmed the nature and orientation of the insertion of RARA into PML. This case underscores the importance of performing alternative testing in FISH-negative cases of APL.