Analysis of NPM1 Gene Mutations in Chinese Adults with Acute Myeloid Leukemia

Abstract

Many European groups have recently described that mutations at exon-12 of the nucleophosmin (NPM1) gene are the most frequent genetic lesion in patients with acute myeloid leukemia (AML), especially in the presence of a normal karyotype. This study explored the prevalence and clinical profile of NPM1 mutations in a cohort of 156 Chinese adults with AML. NPM1 exon-12 mutations were detected using direct sequencing or fragment analysis of genomic DNA polymerase chain reaction products. NPM1 mutations were present in 28.2% of the overall population, including 1/1 (100%) of M₀, 11/27 (40.7%) of M₁, 11/46 (23.9%) of M₂,0/29 (0%) of M₃,2/9 (22.2%) of M₄,18/39 (46.2%) of M₅, and 1/5 (20.0%) of M₆. NPM1 gene mutations were more prevalent in patients with a normal karyotype (37 of 90; 41.1%) when compared with patients with karyotypic abnormalities (7 of 66; 10.6%;P <.001). Sequence analysis of 25 NPM1-mutated cases revealed known mutations (type A, D, N_M, and P_M) as well as one novel sequence variation (here named as type S). All mutational types were heterozygous and showed a 4 bp insertion. NPM1 mutations were significantly associated with old age (P <.05), high peripheral white blood cell count (P <.05), and the subtypes of French-American-British categories M₁/M₅, but negatively associated with expression of CD₃₄ (P <.05) and CD₁₁₇ (P <.05). Thus, this study provides the methods of NPM1 exon-12 mutations detection and related clinical data of NPM1 mutated cases in a Chinese population.