Clinical and genomic characterization of an ATRA-insensitive acute promyelocytic leukemia variant with a FNDC3B::RARB fusion.
Genes Chromosomes Cancer
; 62(10): 617-623, 2023 10.
Article
in En
| MEDLINE
| ID: mdl-37283355
ABSTRACT
The promyelocytic leukemia-retinoic acid receptor-α (PMLRARA) 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 FNDC3BRARB 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Leukemia, Myeloid, Acute
/
Leukemia, Promyelocytic, Acute
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Humans
/
Male
Language:
En
Year:
2023
Type:
Article