Mutational profile of ZBTB16-RARA-positive acute myeloid leukemia.
Cancer Med
; 10(12): 3839-3847, 2021 06.
Article
in En
| MEDLINE
| ID: mdl-34042280
ABSTRACT
BACKGROUND:
The ZBTB16-RARA fusion gene, resulting from the reciprocal translocation between ZBTB16 on chromosome 11 and RARA genes on chromosome 17 [t(11;17)(q23;q21)], is rarely observed in acute myeloid leukemia (AML), and accounts for about 1% of retinoic acid receptor-α (RARA) rearrangements. AML with this rare translocation shows unusual bone marrow (BM) morphology, with intermediate aspects between acute promyelocytic leukemia (APL) and AML with maturation. Patients may have a high incidence of disseminated intravascular coagulation at diagnosis, are poorly responsive to all-trans retinoic acid (ATRA) and arsenic tryoxyde, and are reported to have an overall poor prognosis.AIMS:
The mutational profile of ZBTB16-RARA rearranged AML has not been described so far. MATERIALS ANDMETHODS:
We performed targeted next-generation sequencing of 24 myeloid genes in BM diagnostic samples from seven ZBTB16-RARA+AML, 103 non-RARA rearranged AML, and 46 APL. The seven ZBTB16-RARA-positive patients were then screened for additional mutations using whole exome sequencing (n = 3) or an extended cancer panel including 409 genes (n = 4).RESULTS:
ZBTB16-RARA+AML showed an intermediate number of mutations per patient and involvement of different genes, as compared to APL and other AMLs. In particular, we found a high incidence of ARID1A mutations in ZBTB16-RARA+AML (five of seven cases, 71%). Mutations in ARID2 and SMARCA4, other tumor suppressor genes also belonging to SWI/SNF chromatin remodeling complexes, were also identified in one case (14%). DISCUSSION ANDCONCLUSION:
Our data suggest the association of mutations of the ARID1A gene and of the other members of the SWI/SNF chromatin remodeling complexes with ZBTB16-RARA+AMLs, where they may support the peculiar disease phenotype.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Translocation, Genetic
/
Leukemia, Myeloid, Acute
/
Oncogene Proteins, Fusion
/
Retinoic Acid Receptor alpha
/
Promyelocytic Leukemia Zinc Finger Protein
Type of study:
Prognostic_studies
Limits:
Adult
/
Aged
/
Aged80
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Cancer Med
Year:
2021
Document type:
Article
Affiliation country:
Italy