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Function of retinoid acid receptor agr and p21 in all-trans-retinoic acid-induced acute T-lymphoblastic leukemia apoptosis 

Authors: Peihua Luoa; Meili Lina; Meihua Lina; Yiyu Chenb; Bo Yanga; Qiaojun Hea
Affiliations:   a Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China
b Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China
DOI: 10.1080/10428190902934936
Publication Frequency: 12 issues per year
Published in: journal Leukemia and Lymphoma, Volume 50, Issue 7 July 2009 , pages 1183 - 1189
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Abstract

All-trans-retinoic acid (ATRA) is a morphogenetic signalling molecule derived from vitamin A and is used clinically to target acute promyelocytic leukemia by inducing differentiation of immature blood cells. Retinoid signals are mediated by retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs). Retinoic acid receptors consist of RARagr, RARβ and RARγ isotypes. Among these components, RARagr is preferentially bound to ATRA, which is used to treat acute T-lymphoblastic leukemia, yet the conditions and mechanisms remain unknown. In this study, we have demonstrated that, in human acute T-lymphoblastic leukemia Molt3 cells, inhibition of RA-induced proliferation results from massive cell death characterised by apoptosis. The effect of ATRA:RARagr binding on apoptosis in Molt3 cells has been investigated. Consequently, it has been shown that, in RA-treated Molt3 cells, upregulation of p21 due to RA accompanies caspase 3/PARP activation which precedes the occurrence of apoptosis.
Keywords: ATRA; acute T-lymphoblastic leukemia; RARagr; p21; apoptosis
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