How retinoids kill leukaemic cells

Retinoid hormones affect multiple signal transduction pathways. In clinical trials they have proved beneficial in the treatment of acute promyelocytic leukaemia, but the mechanism of action remains as yet unknown. In May Nature Medicine Lucia Altucci and colleagues from Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, show that induction of Apo-2L/ TRAIL–mediated death signalling appears to contribute to the therapeutic value of retinoids.

Working on NB4 acute promyelocytic leukaemia cells, Altucci et al showed that retinoids selective for retinoic acid receptor-α induced expression of the membrane-bound tumour-selective death ligand, Apo-2L/ TRAIL. In a paracrine fashion, Apo-2L/ TRAIL killed NB4 as well as heterologous and retinoic acid–resistant cells. In the leukaemic blasts of freshly diagnosed acute promyelocytic leukaemia patients, retinoic-acid–induced expression of Apo-2L/ TRAIL caused apoptosis (Nature Med 2001, 7:680-686).

In an accompanying News & Views article Arthur Zelent of Chester Beatty Laboratories, UK suggests that Apo-2L/ TRAIL ...