Evaluation of microRNAs Expression involved in Methylation of ALL and AML

Abstract

Acute leukemia involving lymphocytic and myeloid cells is cancer with a high mortality rate. The swift and timely identification might be a potential approach to improve patient prognosis and survival. The current study was designed to evaluate if the microRNAs (miRNAs) and tumor suppressor genes (TSGs) profiling of hematopoietic bone marrow could help to acute leukemia early detection. Also, we assessed the DNA methyltransferase 3A (DNMT3A) expression and its possible epigenetic effects on miRNAs and TSGs expression levels. The expression levels of ten miRNAs and four TSGs involved in acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) were quantified in 43 and 40 bone marrow samples of ALL and AML patients to comparison with cancer-free subjects by real time quantitative-PCR (RT-qPCR). The receiver-operating-characteristic (ROC) analysis of miRNAs was performed in the study groups. Moreover, the correlation between the DNMT3A and TSGs was calculated. Significant differences were detected in the bone marrow expression of miRNAs and TSGs (P <0.05) between acute leukemia patients and healthy group. ROC analysis confirmed the ability of miR-30a, miR-101, miR-132, miR-129, and miR-143 to discriminate both ALL and AML patients with an area under the ROC curve of ≥0.80 (P <0.001) and high accuracy. Correlation between DNMT3A and P15/P16 TSGs showed that DNMT3A plays vital role in epigenetic control of TSGs expression. Our findings revealed that the downregulation of bone marrow miRNAs and TSGs was accompanied by acute leukemia formation. The authors conclude that this study might prove to introduce useful biomarkers for acute leukemia diagnosis.