Nature Medicine
7, 680 - 686 (2001)
doi:10.1038/89050
Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAILLucia Altucci1, 3, Aurelie Rossin1, Wolfgang Raffelsberger1, Armin Reitmair1, Christine Chomienne2
& Hinrich Gronemeyer11
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, C.U. de Strasbourg, France
2
Institut d'hematology-LBCH, Hôpital St. Louis, Paris, France
3
Istituto di Patologia Generale e Oncologia, Seconda Università degli Studi di Napoli, Napoli, Italy
Correspondence should be addressed to Hinrich Gronemeyer hg@titus.u-strasbg.frThe therapeutic and preventive activities of retinoids in cancer are due to their ability to modulate the growth, differentiation, and survival or apoptosis of cancer cells. Here we show that in NB4 acute promyelocytic leukemia cells, retinoids selective for retinoic-acid receptor- induced an autoregulatory circuitry of survival programs followed by expression of the membrane-bound tumor-selective death ligand, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand, also called Apo-2L). In a paracrine mode of action, TRAIL killed NB4 as well as heterologous and retinoic-acid−resistant cells. In the leukemic blasts of freshly diagnosed acute promyelocytic leukemia patients, retinoic-acid−induced expression of TRAIL most likely caused blast apoptosis. Thus, induction of TRAIL-mediated death signaling appears to contribute to the therapeutic value of retinoids.
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