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

Leukemia & lymphoma

PubMedID: 19557639

Luo P, Lin M, Lin M, Chen Y, Yang B, He Q. Function of retinoid acid receptor alpha and p21 in all-trans-retinoic acid-induced acute T-lymphoblastic leukemia apoptosis. Leuk Lymphoma. 2009;50(7):1183-9.
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 RARalpha, RARbeta and RARgamma isotypes. Among these components, RARalpha 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:RARalpha 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.