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Updated: Jul 7, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
[A study of NPM1 and FLT3 gene mutations in acute myeloid leukemia]
De-pei Wu1, Ling-zhi Yan, Li Yang
1Department of Hematology, the First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou 215006, China. wudepei@medmail.com.cn
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.
Insights
NPM1 and FLT3-ITD mutations are prevalent in acute myeloid leukemia (AML), particularly in patients with normal karyotype. These genetic alterations impact AML characteristics and patient prognosis.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy.
- Genetic mutations, including NPM1 and FLT3-ITD, play crucial roles in AML pathogenesis.
- Understanding mutation prevalence is key for risk stratification and treatment strategies.
Purpose of the Study:
- To determine the frequency of NPM1 gene mutations and FLT3 internal tandem duplication (ITD) mutations in adult AML patients.
- To assess the impact of these mutations on clinical characteristics and patient outcomes.
Main Methods:
- Bone marrow samples from 86 newly diagnosed adult AML patients were analyzed.
- Genomic DNA was extracted and used for Polymerase Chain Reaction (PCR) amplification of NPM1 and FLT3 genes.
- NPM1 exon-12 mutations were detected via capillary electrophoresis, and FLT3-ITD mutations via agarose electrophoresis.
Main Results:
- NPM1 mutations were found in 33.7% and FLT3-ITD mutations in 17.4% of patients.
- Both mutations were more frequent in AML patients with normal karyotype (46.0% and 24.0%, respectively).
- Mutations correlated with higher white blood cell counts and influenced complete remission rates and overall survival, though not always significantly.
Conclusions:
- NPM1 and FLT3-ITD mutations are common in AML, especially in those with normal karyotype.
- These genetic alterations are associated with specific clinical features and prognostic implications in AML patients.
