Cytogenetically cryptic PML::RARA fusion in acute promyelocytic leukemia: Testing strategies in the modern era

•Cytogenetically cryptic PML::RARA fusions is an exceedingly rare phenomenon in acute promyelocytic leukemia•Multiple methodologies may be employed for detecting the cryptic PML::RARA fusion•Concurrent mutations can be identified in cases of acute promyelocytic leukemia with a cryptic PML::RARA fusion; however, a unifying genomic feature remains elusive•For cases with a high clinical suspicion of acute promyelocytic leukemia and no cytogenetic evidence of a PML::RARA fusion, complementary techniques should be employed for further analysis Acute promyelocytic leukemia (APL) is a unique leukemia that is characterized by the PML::RARA fusion. This fusion is often detected by conventional karyotype and fluorescence in situ hybridization (FISH); however, rare cases are cryptic and require molecular techniques to identify the PML::RARA fusion. Furthermore, as the incidence of these cases is rare, analysis by a targeted next-generation sequencing (NGS) panel of myeloid associated genes has never been reported. Herein, a clinical APL case is reported where the PML::RARA fusion was detected only by reverse transcriptase-polymerase chain reaction (RT-PCR), thus underscoring the necessity of utilizing complementary techniques when suspicion for APL is present.