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The retinoic acid receptor that, fused to PML in acute promyelocytic leukaemia, blocks white blood cells from maturing. All-trans retinoic acid releases the block and arsenic trioxide destroys the fusion protein, turning a once rapidly fatal leukaemia into one of the most curable.
RARA is a nuclear receptor that switches on genes of myeloid differentiation when bound by retinoic acid. In acute promyelocytic leukaemia the t(15;17) translocation fuses PML to RARA, and the fusion protein recruits co-repressors that lock promyelocytes in an immature state. Pharmacological doses of all-trans retinoic acid (tretinoin) release the co-repressors and force differentiation, while arsenic trioxide binds the PML moiety and triggers degradation of the fusion protein. Given together, without chemotherapy in standard-risk disease, they cure most patients; differentiation syndrome is the characteristic early complication.
In plain words · The retinoic acid receptor that, fused to PML in acute promyelocytic leukaemia, blocks white blood cells from maturing. All-trans retinoic acid releases the block and arsenic trioxide destroys the fusion protein, turning a once rapidly fatal leukaemia into one of the most curable.
The retinoic acid receptor that, fused to PML in acute promyelocytic leukaemia, blocks white blood cells from maturing. All-trans retinoic acid releases the block and arsenic trioxide destroys the fusion protein, turning a once rapidly fatal leukaemia into one of the most curable.
Ligand-activated nuclear receptor of myeloid differentiation; the PML::RARA fusion in APL is the drug target of tretinoin and arsenic trioxide.
2 products aim at Retinoic acid receptor alpha (RARA): small molecules. Drugs cut off the hormone supply, block the receptor so the hormone cannot bind, or send the receptor to the cell's waste disposal.
Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 4 medicines aimed at it (Tretinoin (all-trans retinoic acid, ATRA), Arsenic trioxide, Acitretin and more) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA RARA: RNA low tissue specificity; no normal tissue stained high. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); Open Targets associates it with 2 specific cancer types at or above 0.5 (acute promyelocytic leukemia, acute myeloid leukemia); the corpus evidence decides and the Open Targets list is quoted for comparison. (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas RARA tissue; Open Targets ENSG00000131759 associations
First described 1987. Earliest sequence paper UniProt cites for the protein: Giguere et al, Nature, 1987, "Identification of a receptor for the morphogen retinoic acid". Source.
Ligand-activated nuclear receptor of myeloid differentiation; the PML::RARA fusion in APL is the drug target of tretinoin and arsenic trioxide.
RNA: low tissue specificity, detected in all normal tissues.
No normal tissue stained high.
No cancer sample stained medium or high.
HPA RARA tissue · HPA RARA pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Acute myeloid leukaemia | about 10% | PML::RARA fusion (acute promyelocytic leukaemia subtype) | PML::RARA is present in nearly all cases of acute promyelocytic leukaemia | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Acitretin is a vitamin A tablet licensed for severe psoriasis. In people who have had an organ transplant and keep developing skin cancers, it reduces the number of new squamous cell carcinomas while it is taken.
Isotretinoin, the acne drug, is given to children with high-risk neuroblastoma for six months after transplant to nudge any surviving cancer cells into growing up into harmless nerve cells. A 1999 trial showed it improved survival and it has been part of standard care since.
Query for this target: (TITLE:"Retinoic acid receptor alpha" OR ABSTRACT:"Retinoic acid receptor alpha" OR TITLE:"RARA" OR ABSTRACT:"RARA") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Retinoic acid receptor alpha (RARA), not a curated reading list.
Shares Tretinoin (all-trans retinoic acid, ATRA), Arsenic trioxide, Acute promyelocytic leukaemia, Acute myeloid leukaemia.
Shares Tretinoin (all-trans retinoic acid, ATRA), Arsenic trioxide, Acute myeloid leukaemia.
Shares Tretinoin (all-trans retinoic acid, ATRA), Arsenic trioxide, Acute promyelocytic leukaemia.
Shares Acitretin, Isotretinoin.
Shares Tretinoin (all-trans retinoic acid, ATRA), Arsenic trioxide, Acute myeloid leukaemia.
Shares Tretinoin (all-trans retinoic acid, ATRA), Arsenic trioxide, Acute myeloid leukaemia.
Shares Tretinoin (all-trans retinoic acid, ATRA), Arsenic trioxide, Acute promyelocytic leukaemia, Acute myeloid leukaemia.