ATRA is a derivative of vitamin A - retinol - which was shown in 1988 to be of value in the treatment of acute promyelocytic leukaemia (APL).
The discovery of ATRA therapy by a group working in Shanghai was mainly due to their inability to afford western cytotoxic agents. As a result, ATRA is now used worldwide as an induction therapy due to excellent rates of complete remission - 95% in patients with chromosomal translocation - and reduced mortality from haemorrhage.
ATRA's role is closely linked to the t[15,17] defect which affects the retinoic acid receptor-alpha (RAR). The exact mechanism of operation is unknown, although it is thought that high intracellular levels of ATRA achieved during therapy allow the abnormal PML/RAR hybrid to adopt a more normal nuclear organization, and thus function is restored. This means that the promyelocyte is able to differentiate which reduces the release of haemorrhagic agents. Further down the differentiation pathway, these treated cells then die by apoptosis.
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