Acute promyelocytic leukaemia: novel insights into the mechanisms of cure.
The fusion oncogene, promyelocytic leukaemia (PML)-retinoic acid receptor-α (RARA), initiates acute promyelocytic leukaemia (APL) through both a block to differentiation and increased self-renewal of leukaemic progenitor cells. The current standard of care is retinoic acid (RA) and chemotherapy, but arsenic trioxide also cures many patients with APL, and an RA plus arsenic trioxide combination cures most patients. This Review discusses the recent evidence that reveals surprising new insights into how RA and arsenic trioxide cure this leukaemia, by targeting PML-RARα for degradation. Drug-triggered oncoprotein degradation may be a strategy that is applicable to many cancers.
Institut National de Santé et de Recherche Médicale, Centre National de Recherche Scientifique, Institut Universitaire d'Hématologie, Université Paris-Diderot UMR 944/7212, Equipe labellisée par Ligue contre Cancer, Service de Biochimie, Hôpital St. Louis, 2 avenue C. Vellefaux, 75475 Paris, CEDEX 10, France. dethe@univ-parisdiderot.fr
Hugues
H
de Thé
Zhu
Z
Chen
D002454:Cell Differentiation; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008954:Models, Biological