- Review
Chronic lymphocytic leukemia (CLL) is a genetically heterogeneous B-cell malignancy in which deletion of chromosome 13q14 [del(13q)] represents the most frequent cytogenetic abnormality. Although isolated del(13q) is traditionally associated with a favourable prognosis, its biological and clinical consequences depend on its underlying genomic context. The DLEU2/miR-15a/16-1 locus within 13q14 represents a key non-coding tumour-suppressive regulatory axis. This review examines the mechanisms underlying miR-15a/16-1 deregulation in CLL and their implications for leukemic biology, clonal evolution, and therapeutic vulnerability. A narrative review of the literature was conducted, focusing on studies addressing the genomic architecture of the 13q14 locus, transcriptional, epigenetic, and post-transcriptional regulation of miR-15a/16-1, validated downstream targets, and the clinical relevance of deletion size, allelic status, deletion burden, and co-occurring cytogenetic lesions. miR-15a/16-1 deregulation results from multilayered mechanisms, including structural heterogeneity of del(13q), altered DLEU2 promoter activity, epigenetic repression, impaired miRNA processing, and subclonal evolution. Reduced cluster expression promotes derepression of key targets involved in apoptosis resistance, cell-cycle progression, and pro-survival signaling, including BCL2, MCL1, CCND1, CDK6, and components of the TP53 and mTOR pathways. The biological effects of del(13q) are further shaped by deletion boundaries, RB1 involvement, clone size, allelic status, and coexisting genomic alterations, including trisomy 12 (+12). The DLEU2/miR-15a/16-1 locus should be considered a dynamic genomic determinant rather than a static favourable-risk lesion. Integrative high-resolution and single-cell approaches may improve the characterization of 13q14 abnormalities and refine biologically informed risk stratification and therapeutic strategies in CLL.
14 November 2026




















![Bodies and minds self-assemble from single cells as a process of alignment and autopoiesis. (A) Most complex biological forms begin as one cell—a fertilized oocyte, commonly thought to be well-described by the laws of physics and chemistry. (B) A gradual, slow process of developmental morphogenesis results in the final form of the organism, which may have complex structure and a mind which may not believe it is a “machine”. Our transformation from a chemical soup into an active embodied mind is continuous but heterogeneous: (C) while we commonly think of ourselves as a unified intelligence with a “centralized” brain, the fact is that even the pineal gland, of which there is only one in the brain, is made of cells (C′) and those cells in turn are made of myriad other active components (C″)—we are a collective intelligence at all scales. (D) The creation of an “individual” out of an excitable medium such as an embryonic blastoderm with hundreds of thousands of cells is a dynamic process that is not hardwired: scratches made in that blastoderm would result in independent self-organization in each island, resulting in multiple embryos forming. This reveals the potentiality for some non-pre-determined number of minds to arise out of the same substrate. Images in (A,B,D) courtesy of Jeremy Guay of Peregrine Creative, used previously in [29]. Image (B) used with permission from [30]. Image in (C′) courtesy of Jose Calvo, Science Photo Library. Image in (C″) courtesy of Evan Ingersoll and Gaël McGill. Image (D) used with permission from [31].](https://mdpi-res.com/philosophies/philosophies-11-00161/article_deploy/html/images/philosophies-11-00161-g001-550.jpg)






