Clinical and genomic characterization of an ATRA-insensitive acute promyelocytic leukemia variant with a FNDC3B::RARB fusion

Genes Chromosomes Cancer. 2023 Oct;62(10):617-623. doi: 10.1002/gcc.23180. Epub 2023 Jun 7.


The promyelocytic leukemia-retinoic acid receptor-α (PML::RARA) fusion is the hallmark of acute promyelocytic leukemia (APL) and is observed in over 95% of APL cases. RARA and homologous receptors RARB and RARG are occasionally fused to other gene partners, which differentially affect sensitivity to targeted therapies. Most APLs without RARA fusions have rearrangements involving RARG or RARB, both of which frequently show resistance to all-trans-retinoic acid (ATRA) and/or multiagent chemotherapy for acute myeloid leukemia (AML). We present a 13-year-old male diagnosed with variant APL with a novel FNDC3B::RARB in-frame fusion that showed no response to ATRA but responded well to conventional AML therapy. While FNDC3B has been identified as a rare RARA translocation partner in ATRA-sensitive variant APL, it has never been reported as a fusion partner with RARB and it is only the second known fusion partner with RARB in variant APL. We also show that this novel fusion confers an RNA expression signature that is similar to APL, despite clinical resistance to ATRA monotherapy.

Keywords: FNDC3B::RARB; RNA-sequencing; acute promyelocytic leukemia (APL); all-trans-retinoic acid (ATRA); exome sequencing; genome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Fibronectins / genetics
  • Genomics
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Promyelocytic, Acute* / drug therapy
  • Leukemia, Promyelocytic, Acute* / genetics
  • Leukemia, Promyelocytic, Acute* / metabolism
  • Male
  • Oncogene Proteins, Fusion / genetics
  • Retinoic Acid Receptor alpha / genetics
  • Translocation, Genetic
  • Tretinoin / therapeutic use


  • Tretinoin
  • Retinoic Acid Receptor alpha
  • Oncogene Proteins, Fusion
  • FNDC3B protein, human
  • Fibronectins