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

Cancer Biol Ther. 2020 Apr 2;21(4):309-314. doi: 10.1080/15384047.2019.1702398. Epub 2020 Jan 20.

Abstract

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.

Keywords: APL; Biallelic CEBPA mutation; Cryptic PML-RARα; Cytogenetics; FISH; RT-PCR.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • Chromosomes, Human, Pair 15 / genetics*
  • Chromosomes, Human, Pair 17 / genetics*
  • Cytogenetic Analysis
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Promyelocytic, Acute / diagnosis*
  • Leukemia, Promyelocytic, Acute / genetics
  • Male
  • Mutation*
  • Oncogene Proteins, Fusion / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Translocation, Genetic*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • Oncogene Proteins, Fusion
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein

Grants and funding

The present study was supported by the Natural Science Foundation of China (grant no. 81760539) and the Science and Technology Plan Project of Jiangxi Provincial Health Planning Commission (grant no. 20171045); National Natural Science Foundation of China [81760539].