Evaluation of growth factor independence 1 expression in patients with de novo acute myeloid leukemia

Objective: Growth factor independence 1 (GFI1), a transcriptional repressor, is required for hematopoietic stem cell maintenance and self-renewal in addition to controlling differentiation and proliferation of myeloid cells. As murine studies have demonstrated that this transcription factor has a notable role in the initiation and progression of acute myeloid leukemia (AML) disease, the aim of the current study was to investigate and review the influence of GFI1 in human AML cells. Methods: GFI1 expression levels were measured by means of real-time polymerase chain reaction in 96 primary AML samples which were then compared to gene expression levels observed in 18 healthy subjects. Moreover, GFI1 expression patterns were analyzed based on specific AML subtypes including acute promyelocytic leukemia (APL). Finally, leukemic cells were stained to measure levels of myeloperoxidase (MPO) activity. Results: This study reports that AML patients have significantly higher GFI1 mRNA levels in comparison to healthy subjects and that, when considering AML subtypes, patients with APL have higher GFI1 expression than non-APL patients. Conclusion: It is also concluded that GFI1 overexpression in patients with high MPO levels, such as those of the APL subtype, is correlated with favorable disease prognosis as supported by other studies which demonstrate that increased peroxide activity and GFI1 are independently correlated with a favorable prognosis

Changes of AML 1 and P53 tumor suppressor gene expression in patients de novo acute myeloid leukemia

P53 and AML1are two important tumor suppressor genes in regulation of hematopoiesis with a critical role in keeping balance between proliferation and differentiation. Alternations in the expression of these genes can be resulted in malignancy. The present study investigated the expression levels of P53 and AML1 genes in 82 de novo AML patient specimens against 12 normal control group using Real-Time-PCR. The results presented in this study revealed that AML1 gene expression was significantly higher and P53 gene expression levels was significantly lower in patients with AML in comparison with the normal control group [P = 0.016 and P = 0.002]. Furthermore, the correlation between P53 and AML1 was significant and positive [P= 0.037 and r= 0.231]. The lower levels of P53 expression were expected and in line with the normal role of this gene as a tumor suppressor gene, however AML1 over expression was in contrast with of its well known role in myeloid maturation. However, this findings suggest that despite the current established role this genes in myeloid cell differentiation, oncogenic form of AML1 [AML1a] has possibly increased and high expression of this isoform may act as an inhibitor for other normal AML1 isoforms and P53 as well