Deregulation of New Cell Death Mechanisms in Leukemia.

Hematological malignancies are among the top five most frequent forms of cancer in developed countries worldwide. Although the new therapeutic approaches have improved the quality and the life expectancy of patients, the high rate of recurrence and drug resistance are the main issues for counteracting blood disorders. Chemotherapy-resistant leukemic clones activate molecular processes for biological survival, preventing the activation of regulated cell death pathways, leading to cancer progression. In the past decade, leukemia research has predominantly centered around modulating the well-established processes of apoptosis (type I cell death) and autophagy (type II cell death). However, the development of therapy resistance and the adaptive nature of leukemic clones have rendered targeting these cell death pathways ineffective. The identification of novel cell death mechanisms, as categorized by the Nomenclature Committee on Cell Death (NCCD), has provided researchers with new tools to overcome survival mechanisms and activate alternative molecular pathways. This review aims to synthesize information on these recently discovered RCD mechanisms in the major types of leukemia, providing researchers with a comprehensive overview of cell death and its modulation.

Involvement of regulated cell deaths in aging and age-related pathologies.

Aging is a pathophysiological process that causes a gradual and permanent reduction in all biological system functions. The phenomenon is caused by the accumulation of endogenous and exogenous damage as a result of several stressors, resulting in significantly increased risks of various age-related diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases. In addition, aging appears to be connected with mis-regulation of programmed cell death (PCD), which is required for regular cell turnover in many tissues sustained by cell division. According to the recent nomenclature, PCDs are physiological forms of regulated cell death (RCD) useful for normal tissue development and turnover. To some extent, some cell types are connected with a decrease in RCD throughout aging, whereas others are related with an increase in RCD. Perhaps the widespread decline in RCD markers with age is due to a slowdown of the normal rate of homeostatic cell turnover in various adult tissues. As a result, proper RCD regulation requires a careful balance of many pro-RCD and anti-RCD components, which may render cell death signaling pathways more sensitive to maladaptive signals during aging. Current research, on the other hand, tries to further dive into the pathophysiology of aging in order to develop therapies that improve health and longevity. In this scenario, RCD handling might be a helpful strategy for human health since it could reduce the occurrence and development of age-related disorders, promoting healthy aging and lifespan. In this review we propose a general overview of the most recent RCD mechanisms and their connection with the pathophysiology of aging in order to promote targeted therapeutic strategies.

HAT1: Landscape of Biological Function and Role in Cancer.

Histone modifications, as key chromatin regulators, play a pivotal role in the pathogenesis of several diseases, such as cancer. Acetylation, and more specifically lysine acetylation, is a reversible epigenetic process with a fundamental role in cell life, able to target histone and non-histone proteins. This epigenetic modification regulates transcriptional processes and protein activity, stability, and localization. Several studies highlight a specific role for HAT1 in regulating molecular pathways, which are altered in several pathologies, among which is cancer. HAT1 is the first histone acetyltransferase discovered; however, to date, its biological characterization is still unclear. In this review, we summarize and update the current knowledge about the biological function of this acetyltransferase, highlighting recent advances of HAT1 in the pathogenesis of cancer.