Background: Nucleophosmin 1 (NPM1) gene is known for its regulatory role of the ARF-p53-tumor suppressor pathway. Its mutations are known to be the most common gene mutations in AML.
Aim: To detect the type of NPM1 gene mutation (NPM-A mut and non-A mut) in AML patients and correlating it with changes in molecular gene expression level of p53 and ARF genes also to study their relation to clinical, laboratory data and response to treatment. Methods: Absolute quantification of the NPM1 mutation type and the expression level of p53 and ARF genes were assessed using quantitative reverse-transcription PCR (RT-qPCR).
Results: We studied 41 newly diagnosed AML patients, all of them had NPM1 gene mutation, out of them 25/41 had non-A mutation (61%) and 16/41 (39%) had mutation A. A statistically significant difference between AML patients with NPM1 mutation-A and non-A mutation was found in bone marrow blasts count (p-value=0.032). A trend statistical significance was observed in patients with NPM1 mutation-A and P53 gene overexpression than in patients with non-A mutation as well as ARF gene expression for patients with NPM1 mutation-A is higher than patients with non-A mutation (p-value=0.063). Median follow up of patients' cohort was 1.81 (0.03-47.1) months. Median survival duration for patients carrying NPM1 mutation-A compared to those with other NPM1 mutations was 1.09 months versus 1.05 months, and this variation lacked statistical significance (p-value of 0.634). Conclusion: We can conclude that there is a trend statistically association between p53 and ARF genes high expression level and NPM1 mut-A type. It is important to detect the type of NPM1 mutation with examination of P53 and ARF genes expression to help in therapeutic strategies.