Home > A. Molecular pathology > RARA

RARA

17q21

Wednesday 2 June 2004

Pathology

Fusion genes by translocation

- PML/RARA fusion gene by t(15;17)(q22;q21) in acute promyelocytic leukemia (APL) (PML at 15q22 and RARA at 17q21).

- NUMA1/RARA fusion gene by t(11;17)(q13;q21) in acute promyelocytic leukemia (APL) (NUMA1 at 11q13 and RARA at 17q21).

- Two translocation events involving the retinoic acid receptor- have been characterized in some detail: PML-RARA and PLZR-RARA.

The leukemia-promoting PML-RARA (promyelocytic leukemia) fusion protein induces hypermethylation and silencing of RAR target genes via the recruitment of HDACs and DNMTase activity.

The induced hypermethylation is linked to oncogenesis and treatment with retinoic acid reverses the transformed phenotype through the induction of target gene demethylation and re-expression.

The promyelocytic leukemia zinc finger (PLZR) protein also associates with transcriptional repressors such as HDACs and PcG proteins and the PLZR-RARA fusion likewise represses genes normally activated by RARA.

In contrast to PML-RARA fusions, PLZR-RARA target genes are insensitive to retinoic acid treatments, despite the fact that retinoic acid does induce PLZR-RARA degradation.

Biomarkers

- Retinoic acid receptor and retinoid X receptor subtype expression for the differential diagnosis of thyroid neoplasms. (19155317)

References

- Retinoic acid receptor and retinoid X receptor subtype expression for the differential diagnosis of thyroid neoplasms. Hoftijzer HC, Liu YY, Morreau H, van Wezel T, Pereira AM, Corssmit EP, Romijn JA, Smit JW. Eur J Endocrinol. 2009 Apr;160(4):631-8. PMID: 19155317