Retinoic acid regulates aberrant nuclear localization of PML-RARα in acute promyelocytic leukemia cells

Karsten Weis, Sophie Rambaud, Catherine Lavau, Joop Jansen, Teresa Carvalho, Maria Carmo-Fonseca, Angus Lamond, Anne Dejean (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

611 Citations (Scopus)

Abstract

Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) translocation that fuses the retinoic acid receptor α (RARα) to a novel gene product, PML. The involvement of RARα is particularly intriguing in view of the efficient therapeutic effect of retinoic acid (RA) in this disease. In this report, we show that PML is specifically localized within a discrete subnuclear compartment corresponding to nuclear bodies recognized by patient autoimmune sera. In APL cells, the PML-RARα hybrid displays an abnormal localization and directs RXR and other nuclear antigens into aberrant structures that are tightly bound to chromatin. This suggests that the hybrid could exert a dominant negative effect by diverting a subset of proteins from their natural sites of action. Interestingly, treatment of APL cells with RA induces a complete relocalization of each of these proteins. We propose that the beneficial role of RA in promoting myeloid differentiation in APL might be related to its ability to restore a normal subnuclear organization.

Original languageEnglish
Pages (from-to)345-356
Number of pages12
JournalCell
Volume76
Issue number2
DOIs
Publication statusPublished - 28 Jan 1994

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