MicroRNAs as New Biomarkers for Diagnosis and Prognosis, and as Potential Therapeutic Targets in Acute Myeloid Leukemia

Abstract

Acute myeloid leukemias (AML) are clonal disorders of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). miRNAs are small non-coding RNAs that regulate, at post-transcriptional level, translation and stability of mRNAs. It is now established that deregulated miRNA expression is a prominent feature in AML. Functional studies have shown that miRNAs play an important role in AML pathogenesis and miRNA expression signatures are associated with chemotherapy response and clinical outcome. In this review we summarized miRNA signature in AML with different cytogenetic, molecular and clinical characteristics. Moreover, we reviewed the miRNA regulatory network in AML pathogenesis and we discussed the potential use of cellular and circulating miRNAs as biomarkers for diagnosis and prognosis and as therapeutic targets.

In vitro knock‐out of miR‐155 suppresses leukemic and HCV virus loads in pediatric HCV‐4–associated acute lymphoid leukemia: A promising target therapy

“…It carries a poor prognosis, especially if it is associated with HCV infection; therefore, we are searching for prognostic and therapeutic biomarkers as an attempt to improve disease outcome. miR‐155 is an oncomiR that is highly expressed in different types of leukemia and lymphoma . In our study, we found very high levels of miR‐155, about seven folds, in HCV_4‐associated ALL in pediatric patients in comparison with the HCV negative leukemic group; moreover, two folds increase in the expression was detected in HCV‐negative leukemic patients in contrast to children with HCV_4 chronic infection.…”

“…miR-155 is an oncomiR that is highly expressed in different types of leukemia and lymphoma. 4,15 In our study, we found very high levels of miR-155, about seven folds, in HCV_4-associated ALL in pediatric patients in comparison with the HCV negative leukemic group; moreover, two folds increase in the expression was detected in HCV-negative leukemic patients in contrast to children with HCV_4 chronic infection. This big difference in the level of expression denotes the oncogenic effect of miR-155 as well as its impact on HCV_4 viral load.…”

“…The different expression of miR‐155 may affect the prognosis and may explain the resistance to the treatment pattern of HCV genotype 4 . On the other hand, studies that investigated the role of miR‐155 in CML and AML demonstrated that it is upregulated in cells and circulating exosomes . There was a negative correlation between the expression of miR‐155 and the response to antiviral drugs; however, a positive correlation with disease progression has been observed .…”

“…14 On the other hand, studies that investigated the role of miR-155 in CML and AML demonstrated that it is upregulated in cells and circulating exosomes. 4,[15][16][17] There was a negative correlation between the expression of miR-155 and the response to antiviral drugs; however, a positive correlation with disease progression has been observed. 18,19 Patients who achieved complete remission showed low levels of miR-155 in the plasma.…”

Low expression of miR‐204 is associated with expression of CD34 and poor performance status in denovo AML

“…12 MicroRNAs are short noncoding single-stranded RNA molecules (19-22 nucleotides) which negatively affect the function of target messenger RNAs post-transcriptionally, modifying many essential cellular functions, including proliferation, differentiation, and death. 13 Many studies have shown that miRNAs may act as oncogenes or tumor suppressors, contributing to the development of malignant cells in both solid and hematological tumors, including AML. 14 It is believed that abnormal expression of some miRNAs may affect the process of development of leukemic cells or alter the response to treatment in cases of AML.…”