FISH, APL, PML/RARA, Translocation 15, 17

Laboratory assay overview

This fluorescence in situ hybridization (FISH) assay uses dual-fusion probes to detect the t(15;17)(q24;q21) translocation that results in the PML/RARA fusion gene. The results of this test may aid in the diagnosis of acute promyelocytic leukemia (APL). APL is a subtype of acute myeloid leukemia with distinct clinical and histopathologic features. Most patients with APL harbor a translocation that involves the RARA gene on chromosome 17 and the PML gene on chromosome 15, which results in a PML/RARA fusion gene [1]. The College of American Pathologists and the American Society of Hematology recommend rapid detection of the PML/RARA fusion gene for patients with suspected APL [2]. A FISH test with dual-fusion probes can be used to detect the PML/RARA fusion gene and help establish the diagnosis. Because a FISH test does not differentiate PML/RARA isotypes, which is needed for subsequent monitoring for measurable residual disease (MRD), a polymerase chain reaction (PCR) test is recommended by the European LeukemiaNet in addition to the FISH test or as an alternative [3]. Approximately 5% of patients with APL harbor variant RARA translocations that involve partner genes other the PML gene [1]. A FISH test with the RARA break-apart probe can be used for assessing the RARA status when morphology is suspicious for APL, but the PML/RARA fusion gene is not detected. A combination of genetic techniques is often involved in identifying genetic abnormalities. FISH testing is complementary to conventional cytogenetic analysis (karyotyping) and can be used to detect common cytogenetic abnormalities. However, because FISH is limited to probing specific chromosomal regions, it does not replace conventional cytogenetic analysis or chromosomal microarray for screening unknown abnormalities. The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings. References 1. Khoury DJ, et al. Myeloid proliferations and neoplasms. In: WHO Classification of Tumours Editorial Board. The World Health Organization Classification of Haematolymphoid Tumours. 5 Beta V2 ed. IARC Press; 2022:chap 2. Accessed June 8, 2023. https://tumourclassification.iarc.who.int 2. Arber DA, et al. Arch Pathol Lab Med. 2017;141(10):1342-1393. 3. Sanz MA, et al. Blood. 2019;133(15):1630-1643.