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.

Iaccarino, L., Ottone, T., Divona, M., Cicconi, L., Cairoli, R., Voso, M.t., et al. (2016). Mutations affecting both the rearranged and the unrearranged PML alleles in refractory acute promyelocytic leukaemia. BRITISH JOURNAL OF HAEMATOLOGY [10.1111/bjh.13910].

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

OTTONE, TIZIANA;VOSO, MARIA TERESA;LO COCO, FRANCESCO
2016-01-05

Abstract

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.
5-gen-2016
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - MALATTIE DEL SANGUE
English
ATRA; ATO resistance; PML and RARA mutations; acute promyelocytic leukaemia; clonal selection
Iaccarino, L., Ottone, T., Divona, M., Cicconi, L., Cairoli, R., Voso, M.t., et al. (2016). Mutations affecting both the rearranged and the unrearranged PML alleles in refractory acute promyelocytic leukaemia. BRITISH JOURNAL OF HAEMATOLOGY [10.1111/bjh.13910].
Iaccarino, L; Ottone, T; Divona, M; Cicconi, L; Cairoli, R; Voso, Mt; LO COCO, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/134521
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