[A study of NPM1 and FLT3 gene mutations in acute myeloid leukemia]

Zhonghua Nei Ke Za Zhi. 2007 Nov;46(11):907-10.
[Article in Chinese]

Abstract

Objective: To evaluate the prevalence and impact of NPM1 gene mutations and FLT3 internal tandem duplication (ITD) mutations in acute myeloid leukemia (AML).

Methods: Mononuclear cells in bone marrow samples were collected from 86 adult patients with newly diagnosed AML. FLT3 and NPM1 genes were amplified with genomic DNA-PCR. NPM1 exon-12 mutations were evaluated with capillary electrophoresis and FLT3-ITD mutations were determined with agarose electrophoresis.

Results: NPM1 gene mutations were identified in 29 of the 86 (33.7%) patients and FLT3-ITD in 15 of the 86 (17.4%) patients. In AML patients with normal karyotype, the frequencies of the two abnormalities were significantly higher than in those without (46.0% and 24.0%, P < 0.05). Both mutations were related to high peripheral white blood cell counts (P < 0.05). WBC counts in the six of the seven cases with NPM1+/FLT3-ITD+ AML were significantly higher (>50 x 10(9)/L). Compared with NPM1(-)AML patients, NPM1(+)AML patients were associated with lower expression of CD(34) (P < 0.001), higher complete remission (CR) rate after initial therapy (66.7% vs 53.3%, P > 0.05) and better overall survival (OS) (P > 0.05), but compared with FLT3-ITD(-)AML patients, FLT3-ITD+ AML patients were associated with lower CR rate (50.0% vs 58.8%; P > 0.05) and worse OS (P > 0.05). The CR rates were 66.7%, 62.5%, 50.0% and 42.9%, respectively, in NPM1+/FLT3-ITD(-), NPM1(-)/FLT3-ITD(-), NPM1+/FLT3-ITD+ and NPM1(-)/FLT3-ITD+AML groups (P > 0.05), but there was no significant differences in OS for four groups.

Conclusions: NPM1 and FLT3-ITD mutations are common in AML patients with normal karyotype and related with the clinical characteristics and prognosis of AML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Female
  • Gene Frequency
  • Humans
  • Karyotyping
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Nuclear Proteins / genetics*
  • Nucleophosmin
  • Prognosis
  • Survival Analysis
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • fms-Like Tyrosine Kinase 3