The expression level of ARF and p53 in AML patients, and their relation to patients' outcome

Abstract

Abstract Background Acute myeloid leukemia (AML) is a cancer of hematopoietic progenitors characterized by gene mutations. The most popular deregulations are mutation and altered expression in the p53 gene, which is considered the guardian of the genome. Its activity is controlled by regulatory genes, e.g., alternate open reading frame (ARF), whose defects could affect p53 activity. Aim To study the effect of altered expression of p53 and ARF genes in de novo AML patients and correlate the results to the patients’ characteristics and outcomes. Methods Expression levels of p53 and ARF were assessed in 96 AML adult patients compared to 20 healthy controls using quantitative reverse-transcription PCR (RT-qPCR). Results There was significant up-regulation of p53 [77.6 (3.8–9528.3)] compared to controls [1.031 (0.210–9.051)], p < 0.001]. The expression level of ARF was significantly upregulated [6.2 (0.5–964.0)] compared to controls [0.854 (0.357–2.519), p < 0.001]. All of the low ARF expressers had low p53 overexpression, 61.1% of patients with high ARF expression had high p53 over-expression, and 38.9% with high ARF expression had low p53 over-expression (p < 0.001). ARF expression shows a trend of association with FLT3 mutation, as 89.3% with FLT3 mutation have high ARF expression (p = 0.080). Low p53 over-expression was seen in 77% of APL patients, while high p53 expression was associated with non-APL (p = 0.040). The median DFS of mutant NPM1 patients was higher than wild NPM1 (46.15 vs. 5.89 days, p = 0.045). Patients aged ≤ 50 years had better OS and DFS than those > 50 (p = 0.05, p = 0.035, respectively).There were no significant statistical associations between DFS and p53, ARF, and FLT3 mutations. Conclusion The p53 and ARF genes are overexpressed in de novo AML patients and they are interrelated. low p53 overexpression is associated with APL phenotype and t(15;17) and patients with t(15;17) had slightly better survival than patients with negative t(15;17) (p = 0.061). AML patients with mutated NPM1 had better DFS than wild NPM1 (p = 0.045). p53 pathway regulation can occur by many alternative ways rather than gene mutation.