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

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 RARα, RARβ and RARγ isotypes. Among these components, RARα 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:RARα 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.