MicroRNA Modulation in Chronic Lymphocytic Leukemia
Summary
MicroRNAs are endogenous regulatory RNAs of approximately 22 nucleotides that fine-tune gene expression by promoting mRNA degradation or inhibiting translation. In chronic lymphocytic leukaemia (CLL), dysregulated microRNA profiles underpin key features of the disease, including malignant B-cell survival, proliferation and resistance to therapy. Loss of tumour-suppressor microRNAs such as the miR-15/16 family leads to unchecked expression of anti-apoptotic proteins, whereas overexpression of oncogenic microRNAs can drive cell cycle progression and evasion of programmed cell death. Distinct microRNA signatures correlate with immunoglobulin heavy-chain variable region (IGHV) mutational status and B-cell receptor (BCR) signalling competence, offering prognostic insight. Aberrant microRNA expression has been linked to resistance to fludarabine and to newer targeted agents, prompting exploration of microRNA-based therapies. Strategies under investigation include restoration of tumour-suppressor microRNAs via synthetic mimics and inhibition of oncogenic microRNAs with antisense oligonucleotides. High-throughput sequencing and integrative bioinformatics have revealed key regulatory clusters, notably the 14q32 locus, as central modulators of the CLL transcriptome. Together, these advances highlight microRNA modulation as both a window into CLL pathogenesis and a platform for novel therapeutic interventions.
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MicroRNA Modulation in Chronic Lymphocytic Leukemia publication trend
The graph below shows the total number of articles in microrna modulation in chronic lymphocytic leukemia across all publications each year (not limited to Nature Index journals).
Technical terms
microRNA: Small non-coding RNA molecule (~22 nucleotides) that regulates gene expression post-transcriptionally by targeting mRNAs for degradation or translational repression.
Chronic lymphocytic leukaemia (CLL): A cancer characterised by accumulation of mature yet dysfunctional B lymphocytes in blood, bone marrow and lymphoid tissues.
IGHV mutational status: Classification of CLL based on somatic hypermutation in the immunoglobulin heavy-chain variable region gene, correlated with clinical outcome.
B-cell receptor (BCR) signalling: Intracellular cascade initiated by antigen binding to surface immunoglobulin on B cells, promoting survival, proliferation and differentiation.
Fludarabine-refractory: State in which CLL no longer responds to the purine analogue fludarabine, often associated with disruptions in p53 signalling and microRNA profiles.
Imprinted locus: Genomic region where gene expression is controlled by parental origin-specific epigenetic marks, affecting co-expressed genes and non-coding RNAs.
References
- Network analysis reveals a major role for 14q32 cluster miRNAs in determining transcriptional differences between IGHV-mutated and unmutated CLL. Leukemia (2023).
- Role of microRNAs in Chronic Lymphocytic Leukemia. International Journal of Molecular Sciences (2023).
- MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia. Molecular Cancer (2010).
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