Resistance to arsenic trioxide and retinoic acid therapy in acute promyelocytic leukemia
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Acute promyelocytic leukemia (APL) is characterized by the reciprocal chromosomal translocation t(15;17)(q22;q21), leading to a fusion of the promyelocytic leukemia gene (PML) on chromosome 15 and the retinoic acid receptor-a gene (RARA) on chromosome 17. Two drugs in clinical use for APL, arsenic trioxide (ATO), and all-trans retinoic acid (ATRA), both act by promoting degradation of PML-RARA. When used as a combination therapy, these drugs lead to durable remission of APL and make it is a highly curable disease .
Recently, two randomized trials conducted by Lo-Coco F et al. and Zhu HH et al. provided strong evidence supporting the use of ATO and ATRA as front-line for APL [1, 2]. However, as ATO and ATRA therapy are more and more widely adopted in treatment for APL, acquired resistance to ATO and ATRA therapy has been recognized in clinical practice.
The C212/213S mutant of the PML, which is thought to be critical for ATO binding, has been described by Jeanne M et al....
KeywordsRetinoic Acid Acute Promyelocytic Leukemia Arsenic Trioxide Acute Promyelocytic Leukemia Cell Acute Promyelocytic Leukemia Patient
Conflict of interest
The authors declare that they have no conflict of interest.
This research work was supported in part by a grant from the Scientific Research Foundation of The Second Hospital of Fujian Medical University, Fujian Province (2012MP13).
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