title: 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.
authors: Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, PR China.
authors: Lingzhi
authors: L
authors: Yan
authors: Suning
authors: S
authors: Chen
authors: Jianying
authors: J
authors: Liang
authors: Yufeng
authors: Y
authors: Feng
authors: Jiannong
authors: J
authors: Cen
authors: Jun
authors: J
authors: He
authors: Weirong
authors: W
authors: Chang
authors: Ziling
authors: Z
authors: Zhu
authors: Jinlan
authors: J
authors: Pan
authors: Yafang
authors: Y
authors: Wu
authors: Yongquan
authors: Y
authors: Xue
authors: Depei
authors: D
authors: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D044466:Asian People / Q000235:genetics; D002681:China; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D015995:Prevalence; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis
chemical_list: D018952:Antigens, CD34; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D019009:Proto-Oncogene Proteins c-kit