Sciaccotta Raffaele, Gangemi Sebastiano, Penna Giuseppa, Giordano Laura, Pioggia Giovanni, Allegra Alessandro
Hematology Unit, Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
Antioxidants (Basel). 2024 Apr 17;13(4):475. doi: 10.3390/antiox13040475.
Chronic lymphocytic leukemia, in spite of recent advancements, is still an incurable disease; the majority of patients eventually acquire resistance to treatment through relapses. In all subtypes of chronic lymphocytic leukemia, the disruption of normal B-cell homeostasis is thought to be mostly caused by the absence of apoptosis. Consequently, apoptosis induction is crucial to the management of this illness. Damaged biological components can accumulate as a result of the oxidation of intracellular lipids, proteins, and DNA by reactive oxygen species. It is possible that cancer cells are more susceptible to apoptosis because of their increased production of reactive oxygen species. An excess of reactive oxygen species can lead to oxidative stress, which can harm biological elements like DNA and trigger apoptotic pathways that cause planned cell death. In order to upset the balance of oxidative stress in cells, recent therapeutic treatments in chronic lymphocytic leukemia have focused on either producing reactive oxygen species or inhibiting it. Examples include targets created in the field of nanomedicine, natural extracts and nutraceuticals, tailored therapy using biomarkers, and metabolic targets. Current developments in the complex connection between apoptosis, particularly ferroptosis and its involvement in epigenomics and alterations, have created a new paradigm.
尽管近年来取得了进展,但慢性淋巴细胞白血病仍然是一种无法治愈的疾病;大多数患者最终会通过复发产生对治疗的耐药性。在慢性淋巴细胞白血病的所有亚型中,正常B细胞内环境稳定的破坏被认为主要是由细胞凋亡缺失引起的。因此,诱导细胞凋亡对于这种疾病的治疗至关重要。活性氧对细胞内脂质、蛋白质和DNA的氧化可导致受损生物成分的积累。癌细胞可能因其活性氧产生增加而更容易发生凋亡。过量的活性氧会导致氧化应激,氧化应激会损害DNA等生物成分并触发导致程序性细胞死亡的凋亡途径。为了打破细胞内氧化应激的平衡,慢性淋巴细胞白血病最近的治疗方法集中在产生活性氧或抑制活性氧上。例子包括纳米医学领域创建的靶点、天然提取物和营养保健品、使用生物标志物的定制疗法以及代谢靶点。细胞凋亡(特别是铁死亡)及其在表观基因组学和改变中的作用之间复杂联系的当前进展创造了一个新的范式。