Identification of a new cryptic PML-RARα fusion gene without t(15;17) and biallelic CEBPA mutation in a case of acute promyelocytic leukemia: a case detected only by RT-PCR but not cytogenetics and FISH.

Acute promyelocytic leukemia (APL) is characterized by the presence of promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion gene, which is formed following the specific chromosomal translocation t(15;17)(q22;q21). However, cases with PML-RARα generated by occult t(15;17) which are negative by both cytogenetics and fluorescence in situ hybridization (FISH), are difficult to diagnose, leading to impaired treatment effectiveness. In the present study, we reported a case of a 66-year-old male patient, and bone marrow morphology, flow cytometry and cytogenetics did not support the diagnosis of APL. Molecular techniques, such as reverse-transcription polymerase chain reaction (RT-PCR), showed the existence of a cryptic PML-RARα fusion gene, and sequence analysis revealed a new variable isoform. Hotspot gene mutation analysis showed a biallelic CEBPA mutation. He received IA chemotherapy and all-trans retinoic acid (ATRA) treatment, and finally achieved complete remission. This case report provided valuable insights into the relevance of the correct identification of atypical PML-RARα fusion gene and biallelic CEBPA mutation. Moreover, combination of IA chemotherapy and ATRA treatment suggested a good clinical effect in this atypical PML-RARα.