THE ROLE OF THE GENETIC ABNORMALITIES, EPIGENETIC AND microRNA IN THE PROGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA (original) (raw)
Related papers
MicroRNA expression in chronic lymphocytic leukaemia
British Journal of Haematology, 2009
patients expressing wild type TP53 . In contrast, p53 levels were not affected in del 17 lymphocytes. Importantly, p21 was not detected in del 17p13.1 lymphocytes suggesting that TP53 is not functional . These results are in agreement with previous reports suggesting that in the majority of CLL patients with malignant lymphocytes displaying del 17p13.1, the remaining TP53 allele is mutated (Zenz et al, 2008).
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.
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.
Brazilian Journal of Pharmaceutical Sciences
The present study evaluated 56 patients diagnosed with Chronic Lymphocytic Leukemia (CLL) and a control group of 44 clinically healthy subjects with no previous history of leukemia. Genetic expressions of AKT and microRNAs were evaluated by quantitative PCR (qPCR). A significant increase in AKT gene expression in patients when compared to controls was observed (p = 0.017). When the patients were stratified according to Binet subgroups, a significant difference was observed between the subgroups, with this protein kinase appearing more expressed in the B+C subgroup (p = 0.013). Regarding miRNA expression, miR-let-7b and miR-26a were reduced in CLL patients, when compared to controls. However, no significant differences were observed in these microRNA expressions between the Binet subgroups (A versus B+C). By contrast, miR-21 to miR-27a oncogenes showed no expression difference between CLL patients and controls. AKT protein kinase is involved in the signaling cascade that occurs with BCR receptor activation, leading to increased lymphocyte survival and protection against the induction of cell death in CLL. Thus, increased AKT protein kinase expression and the reduction of miR-let-7b and miR-26a, both tumor suppressors, may explain increased lymphocyte survival in CLL patients and may be promising markers for the prognostic evaluation of this disease.
Inside the chronic lymphocytic leukemia cell: miRNA and chromosomal aberrations
Molecular Medicine Reports, 2022
alterations in microrna (mirna/mirs) expression are associated with the occurrence and course of human diseases, including chronic lymphocytic leukemia (cll). expression of mirnas may vary among patients with cll in different cytogenetic risk groups. The present study assessed the expression levels of the following mirnas in 35 patients with cll: hsa-mir-15a,-16-1,-29a,-29c,-34a,-34b,-155,-181a,-181b,-221,-222 and-223. Fluorescent in situ hybridization (FiSH) analysis was performed for 13q14d, 17p13 and 11q22 deletions and chromosome 12 trisomy. Significantly higher expression levels of mir-181a,-221 and-223 were observed in the group at low risk of disease progression (stage 0) compared with the group with high risk of cll progression (P=0.036, P=0.019 and P=0.038, respectively). The present study revealed that the expression levels of mirna-181b and miRNA-223 were significantly higher in the group of patients without d13S319 deletion (P=0.039 and P=0.037, respectively). Moreover, the expression levels of mir-15a and mirna-29c were demonstrated to be significantly higher in the group of patients with cll who had a tumor protein p53 deletion, identified by FISH, compared with patients without this lesion (P=0.047, P=0.03 respectively). Based on receiver operating characteristic curve analysis, the present study revealed that mir-181a,-221 and-223 expression was able to distinguish low and high risk of cll progression in patients. among the tested mirnas, mirna-181a,-221 and-223 were indicated to have the greatest diagnostic potential in cll.
Chronic lymphocytic leukemia-associated chromosomal abnormalities and miRNA deregulation
The Application of Clinical Genetics, 2012
Chronic lymphocytic leukemia is the most common leukemia in adults. By cytogenetic investigations major subgroups of the disease can be identified that reflect different routes of tumor development. Of these chromosomal deviations, trisomy 12 and deletions of parts of either the long arm of chromosome 13, the long arm of chromosome 11, or the short arm of chromosome 17 are most commonly detected. In some of these aberrations the molecular target has been identified as eg, ataxia telangiectasia mutated (ATM) in case of deletions of chromosomal region 11q22~23 and the genes encoding microRNAs miR-15a/16-1 as likely targets of deletions of chromosomal band 13q14.3. Of note, these aberrations do not characterize independent subgroups but often coexist within the metaphases of one tumor. Generally, complex aberrations are associated with a worse prognosis than simple karyotypic alterations. Due to smaller sizes of the missing segment the detection of recurrent deletions is not always possible by means of classical cytogenetics but requires more advanced techniques as in particular fluorescence in situ hybridization (FISH). Nevertheless, at this time it is not recommended to replace classical cytogenetics by FISH because this would miss additional information given by complex or secondary karyotypic alterations. However, the results of cytogenetic analyses allow the stratification of prognostic and predictive groups of the disease. Of these, the group characterized by deletions involving TP53 is clinically most relevant. In the future refined methods as eg, array-based comparative genomic hybridization will supplement the existing techniques to characterize CLL.
MicroRNAs as Main Players in the Pathogenesis of Chronic Lymphocytic Leukemia
MicroRNA, 2014
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. The accumulation of mature CD5(+) B-lymphocytes in bone marrow, peripheral blood, and lymphoid organs due to decreased apoptosis is a characteristic of this malignancy. MicroRNAs (miRNAs) are small noncoding RNAs able to regulate the expression of many target genes, including the main apoptosis regulators BCL2 and MCL1. miRNAs play key roles in the pathogenesis of CLL, including specific miRNAs located at the 13q14 chromosomal region that is often deleted or mutated in patients with CLL. In this paper, we review new investigations that underscore the significance of miRNAs for CLL pathogenesis.