Abstract
Simple SummaryThe involvement of miRNAs in physiological cellular processes has been well documented. The development of B cells, which is dictated by a miRNA-transcription factor regulatory network, suggests a typical process partly orchestrated by miRNAs. Besides their contribution in normal hematopoiesis, miRNAs have been severally reported to be implicated in hematological malignancies, a typical example of which is B-cell chronic lymphocytic leukemia (B-CLL). Numerous studies have attempted to highlight the regulatory role of miRNAs in B-CLL or establish some of them as molecular biomarkers or therapeutic targets. Thus, a critical review summarizing the current knowledge concerning the multifaceted role of miRNAs in normal B-cell development and B-CLL progression, prognosis, and therapy, is urgent. Moreover, this review aims to highlight important miRNAs in both normal B-cell development and B-CLL and discuss future perspectives concerning their regulatory potential and establishment in clinical practice.MicroRNAs (miRNAs) represent a class of small non-coding RNAs bearing regulatory potency. The implication of miRNAs in physiological cellular processes has been well documented so far. A typical process orchestrated by miRNAs is the normal B-cell development. A stage-specific expression pattern of miRNAs has been reported in the developmental procedure, as well as interactions with transcription factors that dictate B-cell development. Besides their involvement in normal hematopoiesis, miRNAs are severally implicated in hematological malignancies, a typical paradigm of which is B-cell chronic lymphocytic leukemia (B-CLL). B-CLL is a highly heterogeneous disease characterized by the accumulation of abnormal B cells in blood, bone marrow, lymph nodes, and spleen. Therefore, timely, specific, and sensitive assessment of the malignancy is vital. Several studies have attempted to highlight the remarkable significance of miRNAs as regulators of gene expression, biomarkers for diagnosis, prognosis, progression, and therapy response prediction, as well as molecules with potential therapeutic utility. This review seeks to outline the linkage between miRNA function in normal and malignant hematopoiesis by demonstrating the main benchmarks of the implication of miRNAs in the regulation of normal B-cell development, and to summarize the key findings about their value as regulators, biomarkers, or therapeutic targets in B-CLL.
Highlights
IntroductionB-cell chronic lymphocytic leukemia (B-CLL) is the most common type of leukemia in the Western World affecting mainly elders
B-cell chronic lymphocytic leukemia (B-CLL) is the most common type of leukemia in the Western World affecting mainly elders. It accounts for 7% of non-Hodgkin lymphomas and it is classified as a low-grade B-cell non-Hodgkin lymphoma. It is characterized by the accumulation of abnormal B cells in the blood, bone marrow, lymph and it is classified as a low-grade B-cell non-Hodgkin lymphoma
This study indicated for the first time a potential value of miRNAs as diagnostic and prognostic biomarkers for B-CLL
Summary
B-cell chronic lymphocytic leukemia (B-CLL) is the most common type of leukemia in the Western World affecting mainly elders. Other transcription factors are implicated too, including FOXP1, which controls RAG1 and RAG2 expression [19], and EGR1, a transcriptional regulator essential for B-cell differentiation [20] In this context, miR-191-5p was shown to target Foxp, Tcf, and Egr in mice, exerting a potential controversial role in the developmental procedure since both its deletion and overexpression led to inefficient development of the B cells [21]. Its deficiency in nude mice led to a deregulation of gene expression in mature B cells, due to higher levels of B cell-activating factor receptor (BAFFR; known as TNFRSF13C), which is a direct target of miR-142-5p and enhances B-cell survival, leading to robust B-cell proliferation [40]
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