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  • Title: PML-RARalpha inhibitors (ATRA, tamibaroten, arsenic troxide) for acute promyelocytic leukemia.
    Author: Ohnishi K.
    Journal: Int J Clin Oncol; 2007 Oct; 12(5):313-7. PubMed ID: 17929112.
    Abstract:
    Acute promyelocytic leukemia (APL) is characterized by generation of the PML-RARalpha fusion gene. PML-RARalpha can homodimerize with another PML-RARalpha, and the hybrid binds the histone-deacetylase recruiting co-repressor complex with higher affinity than the wild-type RARalpha. However, the co-repressor complex is releasable by pharmacological doses of all-trans retinoic acid (ATRA). More than 90% of patients with APL achieve a complete remission (CR) with differentiation therapy consisting of ATRA combined with chemotherapy. A new synthetic retinoid, tamibaroten, showed therapeutic effectiveness in patients with ATRA-resistant APL with increased expression of cellular retinoic acid binding protein (CRABP), and about 60% of patients with relapsed APL achieved a CR. Arsenic trioxide triggers the rapid degradation of PML-RARalpha through the targeting of the PML moieties of the fusion protein and showed a high CR rate in relapsed APL. The combination of ATRA, chemotherapy, and/or new agents improved the long-term survival in patients with APL.
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