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 75th 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 miRNA-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 (86.4% and 23.5%, consequently, p = 0.004). The disease free survival was significantly shorter in patients with high miRNA-155 expression compared to those with low expression (median 12 months, 95% CI (7.4 - 15.5) and median notreached, consquenly, p = 0.001). The overall survival was significantly higher (p = 0.002) in patients with low miRNA-155 expression (median overall survival was not reached) compared to patients with high miRNA-155 expression (median overall survival 14.5 months, 95% CI; 10.2 - 17.6). Conclusion: The expression level of miR-155 was significantly higher in AML patients than in control groups and high miRNA-155 expression level was significantly associated with poor cytogenetics, poor response to therapy and shorter disease free and overall survival conferring a poor outcome.