Introduction. Apoptosis, which plays a vital role in regulating the cellular lifespan, is a programmed process distinct from necrosis, which results from physical or chemical injury. The decision to initiate this “cellular suicide” is driven by either intrinsic or extrinsic signals. The extrinsic pathway is triggered by ligands and cytokines binding to death receptors (DRs) located on the cell surface. Conversely, the intrinsic pathway originates from within the mitochondria or the nucleus. These proapoptotic signals initiate a cascade that culminates in the cleavage of specific proteins, ultimately leading to the orderly disassembly of the cell. Objective. The aim of this review is to emphasize that massive apoptosis by overloading phagocytic capacity can trigger an autoimmune reaction through the presentation of nucleosomes to the immune system. Materials and method. In a large cohort study of primary chronic lymphocytic leukemia (CLL), researchers examined samples from over 100 patients to assess their response to MDM2 protein inhibition. The study found a direct correlation between wild-type p53 status protein and the MDM2 inhibitor Nutlin-3 protein, which induces cytotoxicity across various CLL subtypes. In experimental models, disrupting the MDM2-p53 protein interaction restored the p53 function and sensitized tumors to chemotherapy or radiotherapy. However, this response was not observed in malignant B-cell lymphocytes characterized by ZAP-70 and CD38 membrane expression, unmutated immunoglobulin variable genes (IGHV), or mono-allelic ATM gene loss. Results. Proapoptotic signals and death receptors such as TNF-related apoptosis-inducing ligand (TRAIL), tumor necrosis factor (TNF) and the Fas receptor (also known as APO-1 or CD95) are the key adaptor proteins that transmit apoptotic signals. These receptors, known collectively as death receptors (DRs), are also recognized for their role in inducing the autophagy process. Additionally, autoimmune cytopenia (AIC) was observed in patients with high-risk CLL, such as those with unmutated immunoglobulin heavy chain variable region genes (IGHV) or 17p and 11q deletions. Conclusions. The research presented here has a direct impact on clinical patient management, necessitating a shift toward more tailored therapeutic strategies. These findings underscore the need for a personalized medicine approach in clinical practice.
Udriștioiu et al. (Thu,) studied this question.