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The introduction of all-trans retinoic acid, as well as of arsenic trioxide in the treatment of APL, was crucial to achieving the current remarkable cure rates.
The initial evidence of the differentiating properties of retinoic acid and its potential to be used therapeutically came in 1980, first using the HL-60 cell line as a model for APL.
Shortly after the introduction of retinoic acid into the therapy regimen of APL, the need arose for addressing retinoic acid resistance.
Furthermore, up to 50% of patients undergoing treatment will develop differentiation syndrome; a common side effect of differentiating agents.
An evaluation of four clinical trials involving low-risk APL patients from 2010 2014 showed overall survival rates ranging from a low of 86% after three years to a high of 99% after 4 years.
The Jimenez Research Team concluded in their Oncotarget Review, "the biochemical and mechanistic research on APL over the past few decades has led to a unique understanding of this disease and the treatment options, ushering in an era of targeted therapy. Despite remarkable scientific advances in treating APL, some issues still remain, concerning high-risk patients and patients exhibiting an uncharacteristic translocation. The use of HI-60 and NB4 cell lines will continue to be beneficial for future studies on APL since they have already shown a remarkable translational potential and will help address the therapeutic needs of patients that do not respond to conventional treatment. Further studies, addressing aspects of differentiation, nuclear body formation, and degradation of the fusion protein are essential for advancing the treatment of APL and targeting it towards each affected individual. The investigation for alternative therapies for relapsed APL patients and the introduction of clear, defined treatment guidelines in each risk classified group are of particular concern to be addressed." Source:
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