Treatment of acute promyelocytic leukemia with ATRA and As2O3: a model of molecular target-based cancer therapy.

摘要: Most acute promyelocytic leukemia (APL) cases have t(15;17)(q22;q21) chromosomal translocation and PML-RARalpha chimeric gene which blocks granulocytic differentiation. The introduction of all-trans-retinoic acid (ATRA) arsenic compounds, especially trioxide (As(2)O(3)), has provided good models to study not only differentiation and/or apoptosis therapy but also molecular target-based cancer treatment. In vivo in vitro investigations shown that both agents are able induce APL cells: ATRA tends terminal differentiation, while low-dose As(2)O(3) can partial Significant progress been made understanding the mechanisms pathogenesis therapy. Pharmacological concentrations (0.1 approximately 1 microM) derepresses transcription by releasing CoR from, recruiting CoA PML-RARalpha, whereas triggers a rapid degradation PML-RARalpha. fact, two drugs act on same oncoprotein through targeting different moieties distinct ways thereby abrogate its dominant-negative effects regulatory pathways necessary for As apoptosis, it is clear high-dose mitochondria-mediated cell death pathway thiol-dependent manner, mechanism ATRA-induced needs further elucidation. Transcriptomic proteomic analysis expected find new targets. It hope what we learnt from will benefit developments anti-leukemia