Mutations affecting both the rearranged and the unrearranged PML alleles in refractory acute promyelocytic leukaemia

Licia Iaccarino, Tiziana Ottone, Mariadomenica Divona, Laura Cicconi, Roberto Cairoli, Maria Teresa Voso, Francesco Lo-Coco

Research output: Contribution to journalArticle


Acute promyelocytic leukaemia (APL) is characterized by the PML/RARA fusion transcript. PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). We analysed the prevalence of PML mutations in 32 patients with de novo or therapy-related APL (t-APL; n = 5), treated with ATO. We identified one ATO-resistant t-APL patient, who presented a PML A216T mutation in both the rearranged and unrearranged PML alleles, and two mutations in the rearranged RARA gene. In this patient, subclones with different PML and RARA mutations acquired clonal dominance during the disease course, probably leading to treatment resistance.

Original languageEnglish
Pages (from-to)909-913
Number of pages5
JournalBritish Journal of Haematology
Issue number6
Publication statusPublished - Mar 1 2016



  • ATRA
  • Acute promyelocytic leukaemia
  • ATO resistance
  • Clonal selection
  • PML and RARA mutations

ASJC Scopus subject areas

  • Hematology

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