Retinoic acid, but not arsenic trioxide, degrades the PLZF/RARα fusion protein, without inducing terminal differentiation or apoptosis, in a RA-therapy resistant t(11;17)q23;q21) APL patient

Marcel H.M. Koken, Marie Thérèse Daniel, Maurizio Gianni, Arthur Zelent, Jonathan Licht, Agnes Buzyn, Patricia Minard, Laurent Degos, Bruno Varet, Hugues De Thé

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Primary blasts of a t(11;17)(q23;q21) acute promyelocytic leukaemia (APL) patient were analysed with respect to retinoic acid (RA) and arsenic trioxide (As2O3) sensitivity as well as PLZF/RARα status. Although RA induced partial monocytic differentiation ex vivo, but not in vivo, As203 failed to induce apoptosis in culture, contrasting with t(15;17) APL and arguing against the clinical use of As203 in t(11;17)(q23;q21) APL. Prior to cell culture, PLZF/RARα was found to exactly co-localize with PML onto PML nuclear bodies. However upon cell culture, it quickly shifted towards microspeckles, its localization found in transfection experiments. Arsenic trioxide, known to induce aggregation of PML nuclear bodies, left the microspeckled PLZF/RARα localization completely unaffected. RA treatment led to PLZF/RARα degradation. However, this complete PLZF/RARα degradation was not accompanied by differentiation or apoptosis, which could suggest a contribution of the reciprocal RARα/PLZF fusion product in leukaemogenesis or the existence of irreversible changes induced by the chimera.

Original languageEnglish (US)
Pages (from-to)1113-1118
Number of pages6
JournalOncogene
Volume18
Issue number4
DOIs
StatePublished - Jan 28 1999

Keywords

  • Degradation
  • Leukaemia
  • Nuclear dot
  • PML
  • Translocation
  • t(15;17)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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