The Impact of miRNA-155 Expression on Treatment Outcome in Adult Acute Myeloid Leukemia Patients

Abstract

Background: Acute myeloid leukemia is a heterogeneous hematologic malignancy associated with gene mutations, chromosomal rearrangements, deregulation of gene expression and epigenetic modifications. The treatment outcome of AML is highly variable signifying the heterogeneous nature of the disease. Aim of the Study: To evaluate miRNA-155 expression level as a prognostic marker for adult patients with acute myeloid leukemia. Patients and Methods: 101 subjects were included in this study. They were classified into 2 groups, patient group (61 adult patients with newly diagnosed acute myeloid leukemia) and control group (40 apparently healthy adult subjects). miRNA-155 expression was assessed using real time PCR using QIAGEN, miScript, Quanti Tect and Rotor-isc (QIAGEN Group) PAXgene (pre Analytix Gmbh). Samples were either peripheral blood or bone marrow aspiration sample. Results: Roc curve detected 2.85 as best fit value of miRNA-155 for discriminating patients from healthy controls with sensitivity 92.3%, specificity 88.5%, AUC 0.98 and CI (0.96-0.99) (p < 0.001). The 75 th percentile value of the patient group was taken as prognostic cut off value with a value < 9.8 as low miRNA-155 and a value ≥ 9.8 as high miRNA-155. The expression level of miRNA-155 was significantly higher in AML patients than in controls (p = 0.002). Patients with high miRNA expression had a significantly higher white blood cells count (p = 0.002), bone marrow blasts (p = 0.006) and peripheral blood blasts (p = 0.006) compared to patients with low miRNA-155 expression. Patients with poor cytogentics had a significantly higher level of miR-NA-155 expression compared to patients with favorable cytogentics (p = 0.007). The complete remission rate was significantly higher in patients with low miRNA-155 expression compared to those with high expression (86.

Identification of Circulating Micro RNA-155 as a Potential Biomarker for Detecting Acute Myeloid Leukemia

“…In the opposite side of our result, [14] reported that there wasn't significant correlation with miR-155 expression level and LDH without giving any explanation.…”

“…Marcucci [5] reported that at diagnosis of AML cases, high miR-155 expressers had higher percentages of peripheral blood and BM blasts than low expressers with a (P= 0.004 and < 0.001 respectively). Elgohary [14] also reported that there was high significant differences between high and low miR-155 expression levels as regards the percentage of both BM and peripheral blood blast cells (p = 0.006 each). In our study we found that there were no significant correlations between miR-155 gene expression level and age, sex, hemoglobin concentration and platelets count in AML group (P>0.05), this came in concordance with [18] and [14].…”

“…Elgohary [14] also reported that there was high significant differences between high and low miR-155 expression levels as regards the percentage of both BM and peripheral blood blast cells (p = 0.006 each). In our study we found that there were no significant correlations between miR-155 gene expression level and age, sex, hemoglobin concentration and platelets count in AML group (P>0.05), this came in concordance with [18] and [14]. Our studied patients were subdivided according to FAB classification into, M1 (7patients), M2 (10 patients), M4 (7patients) and M5 (1patients), we did not find any significant correlation between miR-155 expression levels and FAB classification (p > 0.05).…”

“…Elgohary [14] study also subdivided patients according to FAB classification into, M2 (13 patients), M4(16 patients) and M5 (23 patients) and did not find any significant difference between miR-155 expression levels and FAB classification (p > 0.05). This goes hand in hand with [15] (p > 0.05).…”

“…These results came in agreement with [5] who reported that the risk of relapse or death of high miR-155 expressers was approximately twice that of the low expressers. Elgohary [14] also reported that there was a highly significant increase in the percentage of patients, who had relapsed during follow up together with increased the percentage of dead patients in high miRNA-155 expression level group compared to those with low miRNA-155 expression level (p < 0.01), also this in agreement with [21]. In our study AML cases with high miR-155 gene expression group showed significantly shorter OS and DFS when compared to low miR-155 gene expression group (OS=91.7% vs 69.2%; mean OS=12.3 vs 9.6 months, (p=0.028); DFS=91.7% vs 25%; mean DFS=11.3 vs 5.9, (p = 0.005).…”