PML-RAR alpha kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy

Simona Sica, L Cicconi, M Divona, C Ciardi, T Ottone, A Ferrantini, S Lavorgna, V Alfonso, F Paoloni, A Piciocchi, G Avvisati, F Ferrara, E Di Bona, F Albano, M Breccia, E Cerqui, M Sborgia, MG Kropp, A Santoro, A LevisS Amadori, MT Voso, F Mandelli, F Lo-Coco

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-alpha (PML-RAR alpha) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARa transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P = 0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RAR alpha transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P = 0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.
Lingua originaleEnglish
pagine (da-a)1987-1992
Numero di pagine6
RivistaLeukemia
Volume30
Stato di pubblicazionePubblicato - 2016

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