Abstract
Background:Acute myeloid leukemia (AML) is a set of Myeloproliferative neoplasms that are identified by excessive growth of myeloid blasts and production of abnormal blood cells. AML is the most common type of acute leukemia that occurs in adults. In addition, AML progresses rapidly and is considered a fatal disease. Thus, there is an urgent need to find new targets for molecularly designed therapies. In This study, we evaluated the circulatory levels of microRNA-29a-3p (miR-29a-3p) and miR-92a-3p beside exploring the expression pattern of their target gene myeloid cell leukemia sequence1 (MCL1) to investigate the role of these molecules in AML pathophysiology and to assess their ability to diagnose AML patients. Methods:40 adult AML patients along with 20 healthy subjects were enrolled in this study. Plasma were separated from venous blood samples, collected on EDTA, of all individuals were used to assess circulating miRNAs’ levels. In the meantime, total RNA was extracted from isolated leukocytes and was used to quantify target mRNA transcript levels. Results:Our data revealed that the circulating levels of miR-29a-3p and miR-92a-3p exhibited significant reduction in 90% and 100% of AML patients, respectively, when compared to the control group (p<0.001). On the other hand, the transcript level of the target gene of these miRNAs, MCL1, showed a sharp increase in 77.5% (p<0.001) of AML patients, along with a negative correlation with its regulatory miRNAs, miR-29a-3p and miR-92a-3p. Conclusion:Our data validates the negative regulatory role of miR-29a-3p and miR-92a-3p to the expression levels of MCL1 in peripheral blood and indicates that these miRNAs can be used as non-invasive diagnostic markers. Furthermore, our study highlights the therapeutic potential of miR-29a-3p and miR-92a-3p to target and downregulate a very important gene (MCL1), which is highly implicated in the pathogenesis of AML.
Highlights
Acute myeloid leukemia (AML) comprises a set of myeloproliferative neoplasms, which are characterized by excessive growth of myeloid blasts and production of abnormal, immature blood cells (Jabbour et al, 2006)
In This study, we evaluated the circulatory levels of microRNA-29a-3p and miR-92a-3p beside exploring the expression pattern of their target gene myeloid cell leukemia sequence1 (MCL1) to investigate the role of these molecules in AML pathophysiology and to assess their ability to diagnose AML patients
Data presented in this study were obtained from the analysis of samples collected from 40 AML patients who were referred to the department of clinical pathology between February 2013 to October 2014
Summary
Acute myeloid leukemia (AML) comprises a set of myeloproliferative neoplasms, which are characterized by excessive growth of myeloid blasts and production of abnormal, immature blood cells (Jabbour et al, 2006). The malignant transformation of the bone marrow progenitor cells in AML results in abnormal production of poorly differentiated myeloid blasts that interfere with the production of normal and functional blood cells (Lane et al, 2009; Khwaja et al, 2016). In This study, we evaluated the circulatory levels of microRNA-29a-3p (miR-29a-3p) and miR-92a-3p beside exploring the expression pattern of their target gene myeloid cell leukemia sequence (MCL1) to investigate the role of these molecules in AML pathophysiology and to assess their ability to diagnose AML patients. The transcript level of the target gene of these miRNAs, MCL1, showed a sharp increase in 77.5% (p
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