Iaccarino Licia, Ottone Tiziana, Divona Mariadomenica, Cicconi Laura, Cairoli Roberto, Voso Maria Teresa, Lo-Coco Francesco
Department of Biomedicine and Prevention, Università di Roma "Tor Vergata", Rome, Italy.
Laboratory of Neuro-Oncohematology, Fondazione Santa Lucia I.R.C.C.S, Rome, Italy.
Br J Haematol. 2016 Mar;172(6):909-13. doi: 10.1111/bjh.13910. Epub 2016 Jan 5.
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.
急性早幼粒细胞白血病（APL）的特征是存在PML/RARA融合转录本。已证明PML和RARA突变对三氧化二砷（ATO）和全反式维甲酸（ATRA）直接有反应。我们分析了32例初发或治疗相关APL（t-APL；n = 5）患者中PML突变的发生率，这些患者接受了ATO治疗。我们鉴定出1例对ATO耐药的t-APL患者，其重排和未重排的PML等位基因均存在PML A216T突变，且重排的RARA基因有两个突变。在该患者中，具有不同PML和RARA突变的亚克隆在病程中获得了克隆优势，这可能导致治疗耐药。
