title: Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype.
abstract: 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-alpha [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.
authors.affiliation: Service d'Hématologie Adulte, Hôpital Saint-Louis, Paris, France. cpreudhomme@chru-lille.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boissel
authors.forename: Aline
authors.initials: A
authors.lastname: Renneville
authors.forename: Valeria
authors.initials: V
authors.lastname: Biggio
authors.forename: Nathalie
authors.initials: N
authors.lastname: Philippe
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Christine
authors.initials: C
authors.lastname: Terre
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tigaud
authors.forename: Sylvie
authors.initials: S
authors.lastname: Castaigne
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Raffoux
authors.forename: Stephane
authors.initials: S
authors.lastname: De Botton
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Herve
authors.initials: H
authors.lastname: Dombret
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics* / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D017384:Sequence Deletion / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3