Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations

• DOI: 10.1038/sj.leu.2404149
• Publication Date: 2006-03-16T10:39:39Z
• Authors: P Gorello; G Cazzaniga; F Alberti; M G Dell'Oro; E Gottardi; G Specchia; G Roti; R Rosati; M F Martelli; D Diverio; F Lo Coco; A Biondi; G Saglio; C Mecucci; B Falini
• Keywords: acute myeloid leukemia; nucleophosmin; NPM; normal karyotype; minimal residual disease; quantitative polymerase chain reaction; Neoplasm, Residual; Reverse Transcriptase Polymerase Chain Reaction; Gene Expression Profiling; DNA Mutational Analysis; Gene Dosage; 610; Nuclear Proteins; acute myeloid leukemia; 3. Good health; Settore MED/15 - MALATTIE DEL SANGUE; 03 medical and health sciences; 0302 clinical medicine; Leukemia, Myeloid; Predictive Value of Tests; 616; Acute Disease; Mutation; minimal residual disease; Humans; nucleophosmin; Nucleophosmin

Mutations in exon 12 of the nucleophosmin (NPM1) gene occur in about 60% of adult AML with normal karyotype. By exploiting a specific feature of NPM1 mutants, that is insertion at residue 956 or deletion/insertion at residue 960, we developed highly sensitive, real-time quantitative (RQ) polymerase chain reaction (PCR) assays, either in DNA or RNA, that are specific for various NPM1 mutations. In all 13 AML patients carrying NPM1 mutations at diagnosis, cDNA RQ-PCR showed >30 000 copies of NPM1-mutated transcript. A small or no decrease in copies was observed in three patients showing partial or no response to induction therapy. The number of NPM1-mutated copies was markedly reduced in 10 patients achieving complete hematological remission (five cases: <100 copies; five cases: 580-5046 copies). In four patients studied at different time intervals, the number of NPM1 copies closely correlated with clinical status and predicted impending hematological relapse in two. Thus, reliable, sensitive RQ-PCR assays for NPM1 mutations can now monitor and quantify MRD in AML patients with normal karyotype and NPM1 gene mutations.