MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin

作者：Lambert Juliette; Lambert Jerome; Nibourel Olivier; Pautas Cecile; Hayette Sandrine; Cayuela Jean Michel; Terre Christine; Rousselot Philippe; Dombret Herve; Chevret Sylvie; Preudhomme Claude; Castaigne Sylvie; Renneville Aline

来源：Oncotarget, 2014, 5(15): 6280-6288.

DOI：10.18632/oncotarget.2196

• minimal residual disease
• gemtuzumab ozogamicin
• acute myeloid leukemia
• WT1 expression
• NPM1 mutation

We analysed the prognostic significance of minimal residual disease (MRD) level in adult patients with acute myeloid leukemia (AML) treated in the randomized gemtuzumab ozogamicin (GO) ALFA-0701 trial. %26lt;br%26gt;Levels of WT1 and NPM1 gene transcripts were assessed using cDNA-based real-time quantitative PCR in 183 patients with WT1 overexpression and in 77 patients with NMP1 mutation (NPM1mut) at diagnosis. %26lt;br%26gt;Positive WT1 MRD (defined as %26gt; 0.5% in the peripheral blood) after induction and at the end of treatment were both significantly associated with a higher risk of relapse and a shorter overall survival (OS). Positive NPM1mut MRD (defined as %26gt; 0.1% in the bone marrow) after induction and at the end of treatment also predicted a higher risk of relapse, but did not influence OS. Interestingly, the achievement of a negative NPM1mut MRD was significantly more frequent in patients treated in the GO arm compared to those treated in control arm (39 % versus 7% (p=0.006) after induction and 91% versus 61% (p=0.028) at the end of treatment). However, GO did not influence WT1 MRD levels. %26lt;br%26gt;Our study supports the prognostic significance of MRD assessed by WT1 and NPM1mut transcript levels and show that NPM1 MRD is decreased by GO treatment.

• 出版日期2014-8-15