Clinical Oncohematology · 2017
Prognostic Value and Correlation Between WT1 Overexpression and NPM1 Mutation in Patients with Acute Myeloblastic Leukemia
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L. L. Girshova, Irina Garmaevna Budaeva, E. G. Ovsyannikova, S. O. Kuzin, D. V. Motorin, R. Sh. Badaev, D. B. Zammoeva, V. V. Ivanov, K. V. Bogdanov, O. S. Pisotskaya, Yu. V. Mirolyubova, T. S. Nikulina, Yu. A. Alekseeva, A. Yu. Zaritskii
Аннотация
Background. Acute myeloblastic leukemia (AML) with NPM1 mutation amounts to 30 % of all AML and is characterized by good prognosis with the exception of cases with FLT3-ITD mutation. Despite the good prognosis, the likelihood of relapses in patients with NPM1 mutation may significantly differ. Thus, the estimation of the minimal residual disease (MRD) after chemotherapy and during follow-up is becoming increasingly important. This approach will make it possible to predict the sensitivity of a tumoral clone to chemotherapy. Aim. To evaluate the prognostic value of highly specific marker (NPM1 mutation) and non-specific marker (WT1 overexpression) of MRD, as well as to identify the correlation between the levels of NPM1 and WT1 at different stages of therapy and in the follow-up period. Materials & Methods. The research included 14 patients with AML. All patients had the NPM1 mutation and WT1 overexpression: 50 % of patients had additional molecular markers (BAALC overexpression, FLT3-ITD, DNMT3A, and MLL mutations). Real-time PCR was used for long-term monitoring of WT1 expression levels and NPM1 mutation. Results. The median decrease of NPM1 levels after the induction therapy was 3 log. All patients had relapses, NPM1 mutation, and lower rates of OS/RFS, which significantly correlated with prognostically negative molecular markers. There were no statistically significant differences in RFS in groups with the decrease of WT1 expression level 2 log on day 28 of treatment. At the same time, the decrease of WT1 expression by > 2 log was associated with significant differences in early relapses, which correlated with the decrease of NPM1 levels (> and 3 log on day 28. The decrease in WT1 expression of