All-trans retinoic acid
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All-trans retinoic acid (ATRA) is a drug used for the treatment of acute promyelocytic leukemia (APML, AML subtype M3). It is marketed as Vesinoid®.
It is usually prescribed over 3 months at about 8 capsules per day. There are now other forms available.
ATRA is a form of vitamin A, and has similar side-effects (e.g. benign intracranial hypertension). Its success in treating acute promyelocytic leukemia was a major breakthrough in the treatment of this type of leukemia. It works in APML because the majority of cases involve a chromosomal translation of chromosomes 15 and 17, which causes genetic fusion of the retinoic acid receptor (RAR) gene to the promyelocytic leukemia (PML) gene. This fusion PML-RAR protein is responsible for preventing immature myeloid cells from differentiating into more mature cells. This block in differentiation is thought to cause leukemia. ATRA acts on PML-RAR to lift this block, causing the immature promyelocytes to differentiate to normal mature blood cells.
ATRA is associated with the unique complication of retinoic acid syndrome in patients with acute promyelocytic leukemia. This is associated with the development of dyspnea, fever, weight gain, peripheral edema and is treated with dexamethasone. The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome from cytokine release from the differentiating promyelocytes.
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