ATRA

All-trans retinoic acid (ATRA), also known as tretinoin, is a retinoid and active metabolite of vitamin A used in medicine for differentiation therapy in acute promyelocytic leukemia (APL) and as a topical treatment for certain dermatologic conditions. It is available in systemic forms for cancer and topical formulations for skin disorders.

In acute promyelocytic leukemia, ATRA binds to retinoic acid receptors, particularly RARα, to counteract the PML–RARα fusion protein produced by the t(15;17) translocation. This interaction promotes differentiation of malignant promyelocytes and helps restore normal hematopoiesis. ATRA is commonly used in combination with arsenic trioxide or chemotherapy and has contributed to improved remission and survival rates in APL.

Topically, tretinoin is used to treat acne vulgaris and to improve signs of photoaging by promoting epidermal turnover and collagen remodeling. It is available in various concentrations as creams, gels, and solutions, and treatment regimens are tailored to the patient’s skin type and condition.

Mechanistically, ATRA acts as a ligand for nuclear retinoic acid receptors, regulating gene expression to promote differentiation and apoptosis in abnormal cells. In APL, this helps overcome the differentiation arrest caused by the fusion protein, enabling maturation of leukemic cells.

Adverse effects include differentiation syndrome in systemic use, characterized by fever, respiratory symptoms, edema, and hypotension, as well as risks of hepatotoxicity and hyperleukocytosis. Topical retinoids commonly cause local irritation, erythema, dryness, and photosensitivity. Systemic use is teratogenic, necessitating contraception during treatment and for a period after therapy.

History and availability: ATRA is marketed under various names for APL therapy in many countries and is also used as topical tretinoin for dermatologic indications.