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Barragan, E. et al.

Eva Barragan, Juan C. Pajuelo, Sandra Ballester, Oscar Fuster, Jose Cervera, Federico Moscardo, Leonor Senent, Esperanza Such, Miguel A. Sanz, Pascual Bolufer,

Minimal residual disease detection in acute myeloid leukemia by mutant nucleophosmin (NPM1): comparison with WT1 gene expression.

BACKGROUND: Molecular analysis of minimal residual disease is only applicable in acute myeloblastic leukemia (AML) patients with genetic markers (20-30%). This study analyzes the feasibility of the real-time quantitative polymerase chain reaction (RQ-PCR) assay to detect mutant nucleophosmin (NPM1) during follow-up in AML patients. Moreover, we compare the NPM1 results with those of WT1 expression to MRD assessment. METHODS: The study includes 97 samples from 24 AML patients with type A NPM1 mutation at diagnosis. MRD was evaluated simultaneous by RQ-PCR assay to detect NPM1-mutated and WT1 expression. RESULTS: The expression levels of WT1 and NPM1 in 93 paired samples showed a strong positive correlation (r=0.81; p<0.0001). However, the kinetics of disappearance were different, WT1 decreased rapidly after induction but maintained these residual levels after treatment in patients in complete remission, whereas NPM1 experienced a mild reduction after induction but was undetectable in long survivor patients. CONCLUSIONS: This study shows the feasibility of the RQ-PCR assay to monitor MRD in AML patients carrying NPM1 mutations and its advantage over RQ-PCR assay for WT1. Owing to NPM1-mutated is specific of leukemic cells and shows higher levels at presentation.[1]

References

Minimal residual disease detection in acute myeloid leukemia by mutant nucleophosmin (NPM1): comparison with WT1 gene expression. Barragan, E., Pajuelo, J.C., Ballester, S., Fuster, O., Cervera, J., Moscardo, F., Senent, L., Such, E., Sanz, M.A., Bolufer, P. Clin. Chim. Acta (2008) [Pubmed]

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