Acute myeloid leukemia (AML) establishes an immunosuppressive microenvironment that favors leukemic proliferation. The immune-suppressive cytokines altered antigen processing, and presentation collectively assist AML cells in escaping cytotoxic T-cell surveillance. These CD8⁺ T cell dysfunction features are emerging therapeutic targets in relapsed/refractory AML patients. Besides, CD8⁺ T cell exhaustion is a hotspot in recent clinical oncology studies, but its pathophysiology has yet to be elucidated in AML. In this review, we summarize high-quality original studies encompassing the phenotypic and genomic characteristics of T cell exhaustion events in the leukemia progression, emphasize the surface immuno-peptidome that dynamically tunes the fate of T cells to function or dysfunction states, and revisit the biochemical and biophysical properties of type 1 MHC antigen processing mechanism (APM) that pivots in the phenomenon of leukemia antigen dampening.

Senescence-resumed proliferation (SRP) is proposed to be a mechanism associated with the escape of p21-mediated senescence and the activation of Wnt/β-catenin pathways that enhance malignancy. The keloid genomic landscape shows heavy intersections between TP53 and TGF-β signaling. The machinery to maintain cellular integrity through senescence, apoptosis, and autophagy is co-regulated with stemness, hedgehog, and immunomodulation. Our study demonstrated the presence of SRP and how, on the transcriptome level, TP53 and Wnt/β-catenin pathways are regulated to deliver the same cellular fate. Our study proves that SRP co-regulated with senescence-associated reprogramming (Wnt/β-catenin pathways) and TP53-p21 dysregulations originate from a common etiology and present a novel therapeutic target opportunity.

Inherited retinal dystrophies (IRDs) constitute a heterogeneous group of primarily monogenic orphan diseases caused by mutations in over 300 genes, collectively affecting millions of individuals worldwide with visual impairment. Despite significant advances, the development of gene replacement therapy for IRDs has predominantly focused on single‐gene approaches, lacking a unified strategy driven by factors such as global prevalence, disease burden, and feasibility of therapeutic delivery. In this review, we propose a comprehensive protocol integrating multifaceted methodologies to refine the identification of suitable gene therapy candidates. We assessed gene prevalence, transcript size compatibility with vector packaging, and cell‐type–specific expression, enabling the prioritization of promising therapeutic targets. Our approach focuses on assessing enzyme‐coding genes as prime, more suitable candidates for therapeutic intervention due to their relatively similar replacement mechanism. Our findings provide a framework for identifying additional genes that may benefit from similar translational pipelines. This approach revealed a spectrum of potential candidates, including several underexplored genes with high therapeutic potential. Our findings underscore the necessity of adopting a strategic, data‐driven framework to prioritize clinically impactful and scalable gene therapy targets, paving the way for broader and more effective therapeutic applications in the field of IRDs. Trial Registration: ClinicalTrials.gov identifier: NCT01482195, NCT03316560, NCT06333249, NCT06275620, NCT04850118, NCT05926583