Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype

• Published in: Blood Vol. 106; no. 10; pp. 3618 - 3620
• Main Authors: Boissel, Nicolas, Renneville, Aline, Biggio, Valeria, Philippe, Nathalie, Thomas, Xavier, Cayuela, Jean-Michel, Terre, Christine, Tigaud, Isabelle, Castaigne, Sylvie, Raffoux, Emmanuel, De Botton, Stephane, Fenaux, Pierre, Dombret, Herve, Preudhomme, Claude
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.11.2005; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; CCAAT-Enhancer-Binding Protein-alpha - genetics; CCAAT-Enhancer-Binding Protein-alpha - metabolism; Exons - genetics; Female; fms-Like Tyrosine Kinase 3 - genetics; fms-Like Tyrosine Kinase 3 - metabolism; Hematologic and hematopoietic diseases; Humans; Karyotyping; Leukemia, Myeloid, Acute - blood; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocyte Count; Male; Medical sciences; Middle Aged; Mutagenesis, Insertional; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Predictive Value of Tests; Prevalence; Prognosis; Risk Factors; Sequence Deletion - genetics; Human; Prognosis; Prevalence; Nucleophosmin; Acute; Cytogenetics; Clinical form; Genetics; Malignant hemopathy; Mutation; Karyotype; Acute myelocytic leukemia
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-05-2174

Mutation of the nucleophosmin (NPM) gene has been reported as the most frequent mutation in acute myeloid leukemia (AML), especially in the presence of a normal karyotype. In this subgroup of intermediate-risk AML, the identification of other gene mutations (eg, FLT3, CCAAT/enhancer-binding protein-α [CEBPA]) has helped to refine the prognosis. This study explored the prevalence and the prognostic impact of NPM mutations in a cohort of 106 patients with normal-karyotype AML. NPM exon 12 mutations were detected by polymerase chain reaction (PCR) and fragment analysis for the insertion/deletion globally resulting in a 4-bp insertion. NPM mutations were detected in 47% of patients and were associated with a high white blood cell count, involvement of the monocytic lineage (M4/M5), and a decreased prevalence of CEBPA mutations. Complete remission rate and long-term outcome did not differ between NPM-mutated and -nonmutated patients. Prospective studies are needed to confirm the definitive place of NPM mutation detection to predict AML response to therapy.