Comparison of microRNA expression in high-count monoclonal B-cell lymphocytosis and Binet A chronic lymphocytic leukemia (original) (raw)
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Purpose: Despite its indolent nature, chronic lymphocytic leukemia (CLL) remains an incurable disease. To establish the potential pathogenic role of miRNAs, the identification of deregulated miRNAs in CLL is crucial.Experimental Design: We analyzed the expression of 723 mature miRNAs in 217 early-stage CLL cases and in various different normal B-cell subpopulations from tonsils and peripheral blood.Results: Our analyses indicated that CLL cells exhibited a miRNA expression pattern that was most similar to the subsets of antigen-experienced and marginal zone–like B cells. These normal subpopulations were used as reference to identify differentially expressed miRNAs in comparison with CLL. Differences related to the expression of 25 miRNAs were found to be independent from IGHV mutation status or cytogenetic aberrations. These differences, confirmed in an independent validation set, led to a novel comprehensive description of miRNAs potentially involved in CLL. We also identified miRN...
miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia
Brazilian Journal of Medical and Biological Research, 2007
MicroRNAs (miRNAs) are a class of small endogenous RNAs that play important regulatory roles by targeting mRNAs for cleavage or translational repression. miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their association with cancer. We determined the miRNA expression profile of chronic and acute lymphocytic leukemias (CLL and ALL) using the TaqMan ® MicroRNA Assays Human Panel (Applied Biosystems). Pooled leukemia samples were compared to pooled CD19 + samples from healthy individuals (calibrator) by the 2 -∆∆Ct method. Total RNA input was normalized based on the Ct values obtained for hsa-miR-30b. The five most highly expressed miRNAs were miR-128b, miR-204, miR-218, miR-331, and miR-181b-1 in ALL, and miR-331, miR-29a, miR-195, miR-34a, and miR-29c in CLL. To our knowledge, this is the first report associating miR-128b, miR-204 and miR-331 to hematological malignancies. The miR-17-92 cluster was also found to be up-regulated in ALL, as previously reported for some types of lymphomas. The differences observed in gene expression levels were validated for miR-331 and miR-128b in ALL and CD19 + samples. These miRNAs were upregulated in ALL, in agreement with our initial results. A brief target analysis was performed for miR-331. One of its putative targets, SOCS1, promotes STAT activation, which is a known mediator of cell proliferation and survival, suggesting the possibility of an association between miR-331 and these processes. This initial screening provided information on miRNA differentially expressed in normal and malignant B-cells that could suggest the potential roles of these miRNAs in hematopoiesis and leukemogenesis.
2014
Purpose: Despite its indolent nature, chronic lymphocytic leukemia (CLL) remains an incurable disease. To establish the potential pathogenic role of miRNAs, the identification of deregulated miRNAs in CLL is crucial. Experimental Design: We analyzed the expression of 723 mature miRNAs in 217 early-stage CLL cases and in various different normal B-cell subpopulations from tonsils and peripheral blood. Results: Our analyses indicated that CLL cells exhibited a miRNA expression pattern that was most similar to the subsets of antigen-experienced and marginal zone-like B cells. These normal subpopulations were used as reference to identify differentially expressed miRNAs in comparison with CLL. Differences related to the expression of 25 miRNAs were found to be independent from IGHV mutation status or cytogenetic aberrations. These differences, confirmed in an independent validation set, led to a novel comprehensive description of miRNAs potentially involved in CLL. We also identified miRNAs whose expression was distinctive of cases with mutated versus unmutated IGHV genes or cases with 13q, 11q, and 17p deletions and trisomy 12. Finally, analysis of clinical data in relation to miRNA expression revealed that miR26a, miR532-3p, miR146-5p, and miR29c à were strongly associated with progressionfree survival. Conclusion: This study provides novel information on miRNAs expressed by CLL and normal B-cell subtypes, with implication on the cell of origin of CLL. In addition, our findings indicate a number of deregulated miRNAs in CLL, which may play a pathogenic role and promote disease progression. Collectively, this information can be used for developing miRNA-based therapeutic strategies in CLL. Clin Cancer Res; 20(15); 4141-53. Ó2014 AACR.
Role of microRNAs in chronic lymphocytic leukemia (Review)
Molecular medicine reports, 2013
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in the western world. It is characterized by a malignant clone of B cells in the bone marrow, blood and secondary lymphoid tissues. microRNAs (miRNAs) are a family of small, non‑coding RNAs that regulate the expression of target messenger RNAs at the post‑transcriptional level. Previous studies have suggested that miRNAs are extensively involved in the proliferation and differentiation of hematopoietic cells. Aberrant expression of certain miRNAs has been observed in CLL. Associations between miRNAs and chromosomal abnormalities suggest that miRNAs may be involved in the pathogenesis of CLL. Moreover, miRNAs may be used as novel biomarkers for the prognosis of CLL. Expression levels of miRNAs are also involved in resistance to chemotherapy drugs. In this article, we review recent developments of miRNAs in the initiation, prognosis and chemoresistance of CLL.
Serum Expression of Seven MicroRNAs in Chronic Lymphocytic Leukemia Patients
Journal of Blood Medicine, 2020
Purpose: MicroRNAs are small single-strand noncoding RNAs that can be deregulated in a variety of cancers. Over the past few years, multiple markers have been discovered in chronic lymphocytic leukemia (CLL). Among these, miRNAs seem to have important roles in the pathogenesis of CLL. The development and validation of miRNA-expression patterns as biomarkers should have a significant impact in cancer diagnosis, therapeutic success, and increasing the life expectancy of patients. In this study, to specify the utility of circulatory miRNA expression as noninvasive and useful biomarkers for CLL, we analyzed the dysregulation of seven miRNAs: miR30d, miR25-3p, miR19a-3p, miR133b, miR451a, miR145, and miR144 in CLL-patient sera. Methods: Thirty untreated patients with flow-cytometry confirmation of CLL were chosen. Serum samples were collected from 30 newly diagnosed CLL patients. Fifteen healthy samples were taken for comparison as controls. RNA was extracted using Trizol. RNA from CLL patient specimens was compared to controls with real-time PCR. Results: Seven miRNAs were differently expressed between CLL and normal specimens using the comparative 2 −ΔΔ Ct method. miRNAs 133b, 25-3p, 451a, 145, 19a-3p, and 144 were overexpressed in sera obtained from CLL patients, and miRNA-30d was underexpressed in patient samples. Among these seven miRNAs, miR19a-3p and miR25-3p showed the most deregulation in CLL patients. Conclusion: Real-time PCR is an applied means to perform high-throughput investigation of serum-RNA samples. We assessed the expression of seven miRNAs in CLL patients by this method. The results demonstrated that the use of miRNA-expression profiling may have an impressive role in the diagnosis of CLL. In addition, miRNA 19a-3p and 25-3p are known oncogenes with therapeutic and potential biomarkers.
MicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia
Proceedings of the National Academy of Sciences, 2011
Early cancer detection and disease stratification or classification are critical to successful treatment. Accessible, reliable, and informative cancer biomarkers can be medically valuable and can provide some relevant insights into cancer biology. Recent studies have suggested improvements in detecting malignancies by the use of specific extracellular microRNAs (miRNAs) in plasma. In chronic lymphocytic leukemia (CLL), an incurable hematologic disorder, sensitive, early, and noninvasive diagnosis and better disease classification would be very useful for more effective therapies. We show here that circulating miRNAs can be sensitive biomarkers for CLL, because certain extracellular miRNAs are present in CLL patient plasma at levels significantly different from healthy controls and from patients affected by other hematologic malignancies. The levels of several of these circulating miRNAs also displayed significant differences between zeta-associated protein 70 (ZAP-70) + and ZAP-70 − CLL. We also determined that the level of circulating miR-20a correlates reliably with diagnosis-totreatment time. Network analysis of our data, suggests a regulatory network associated with BCL2 and ZAP-70 expression in CLL. This hypothesis suggests the possibility of using the levels of specific miRNAs in plasma to detect CLL and to determine the ZAP-70 status.
Molecular medicine (Cambridge, Mass.), 2013
Critical processes of B-cell physiology, including immune signaling through the B-cell receptor (BcR) and/or Toll-like receptors (TLRs), are targeted by microRNAs. With this in mind and also given the important role of BcR and TLR signaling and microRNAs in chronic lymphocytic leukemia (CLL), we investigated whether microRNAs could be implicated in shaping the behavior of CLL clones with distinct BcR and TLR molecular and functional profiles. To this end, we examined 79 CLL cases for the expression of 33 microRNAs, selected on the following criteria: (a) deregulated in CLL versus normal B-cells; (b) differentially expressed in CLL subgroups with distinct clinicobiological features; and, (c) if meeting (a) + (b), having predicted targets in the immune signaling pathways. Significant upregulation of miR-150, miR-29c, miR-143 and miR-223 and downregulation of miR-15a was found in mutated versus unmutated CLL, with miR-15a showing the highest fold difference. Comparison of two major sub...
Cancers
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, p...