Acute Promyelocytic Leukemia with Rare Genetic Aberrations: A Report of Three Cases

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) that is characterized by the PML::RARA fusion or, more rarely, a variant RARA translocation. While APL can be clinically suspected, diagnosis of APL requires genetic confirmation. Targeted therapy such as all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has dramatically improved the prognosis of APL patients, but this is dependent on timely genetic testing as different fusions and/or mutations can affect therapeutic outcomes. Here we report three APL cases with various genetic aberrations: cryptic PML::RARA fusion, variant RARA rearrangement, and typical PML::RARA fusion with co-existing FLT3-ITD mutation. They serve to illustrate the utility of integrating genetic testing, using chromosome analysis, fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and next-generation sequencing (NGS) in providing a detailed understanding of the genetic alterations underlying each patient’s disease.