Monitoring minimal residual disease in acute myeloid leukaemia with NPM1 mutations by quantitative PCR: clonal evolution is a limiting factor.
Br J Haematol
; 144(4): 517-23, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-19055671
ABSTRACT
Nucleophosmin (NPM1) mutations in exon 12 represent the most frequent molecular aberrations in adult patients with acute myeloid leukaemia (AML). Molecular detection of NPM1 mutation A could be a useful marker for routine monitoring of minimal residual disease (MRD). We established a calibrator-normalized relative quantification real-time polymerase chain reaction (PCR) assay for NPM1 mutation A. ABL1 was used as a reference housekeeping gene and the NPM1 mutation A-containing OCI/AML3 cell line as a calibrator. Relative quantification was performed by calculating the NPM1 mutation A/ABL1 ratio which was normalized to the NPM1 mutation A/ABL1 ratio of OCI/AML3 calibrator cDNA. The assay showed a sensitivity of 10(-5). The clinical usefulness was evaluated by monitoring MRD in 51 AML patients with NPM1 mutation A. In 27 patients analysed at diagnosis and after induction treatment, NPM1 mutation A ratios showed a median log(10) reduction of 2.48, which correlated with response to therapy. Among the 51 patients, 21 relapsed and two lost the mutation. We established a sensitive, specific and reproducible assay for routine quantification and monitoring of NPM1 mutation A levels. However, clonal evolution was observed in 9.5% limiting the usefulness of the NPM1 mutation A mutation as a molecular marker in these patients.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Leucemia Mieloide Aguda
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Mutação
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article