Abstract
Tumor suppressors play an important role in cancer pathogenesis and in the modulation of resistance to treatments. Loss of function of the proteins encoded by tumor suppressors, through genomic inactivation of the gene, disable all the controls that balance growth, survival, and apoptosis, promoting cancer transformation. Parallel to genetic impairments, tumor suppressor products may also be functionally inactivated in the absence of mutations/deletions upon post-transcriptional and post-translational modifications. Because restoring tumor suppressor functions remains the most effective and selective approach to induce apoptosis in cancer, the dissection of mechanisms of tumor suppressor inactivation is advisable in order to further augment targeted strategies. This review will summarize the role of tumor suppressors in chronic lymphocytic leukemia and attempt to describe how tumor suppressors can represent new hopes in our arsenal against chronic lymphocytic leukemia (CLL).
Highlights
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world accounting for 25% of all adult leukemias [1]
In the first part of this review, we describe the genetic impairment of tumor suppressors in chronic lymphocytic leukemia (CLL) through mutations and deletions, as found for various TP53, ataxia telangiectasia mutated (ATM), and others
MiR-15a and miR-16-1 inhibit the expression of B cell CLL/B-cell lymphoma 2 (BCL2), as well as the cyclins Cyclin D1 (CCND1) and CCND3, and cyclin-dependent kinase 6 (CDK6) [18]
Summary
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world accounting for 25% of all adult leukemias [1] In these countries, the incidence of CLL is almost. Cancers 2020, 12, 629 it is crucial to well-stratify CLL patients with the aim of identifying those who can really benefit from a chemotherapy approach (e.g., immunoglobulin heavy chain variable region gene IGHV-mutated) and who cannot (e.g., tumor protein p53, TP53-mutated). The portrait of the CLL genome has been taken with great detail, in either coding or non-coding compartments [12,13,14] Overall, these great efforts have pointed out that the number of copy number aberrations is low, with a range of 0–2 lesions per patient, suggesting that complex mechanisms may promote CLL development and maintenance, besides genetics. We describe tumor suppressors that are functionally inactivated, including modifications at the transcriptional and protein levels
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