Moqattash Satei, Lutton John D
Department of Human and Clinical Anatomy, College of Medicine, Sultan Qaboos University, Muscat, Sultanate of Oman.
Exp Biol Med (Maywood). 2004 Feb;229(2):121-37. doi: 10.1177/153537020422900201.
The network and balance of cytokines is of major importance in maintaining proper homeostasis of hematopoiesis. Abnormalities in this network may result in a variety of blood disorders; however, the role of this network is not clear in leukemia. The use of antineoplastic agents has improved the survival rate of some types of leukemia, and adjunctive therapy with cytokines may be helpful. Chemotherapeutic approaches are no longer the best choice because cytotoxicity may affect normal and leukemic cells, and leukemic cells may develop resistance to the chemotherapeutic agent. Induction of differentiation to a mature phenotype and the control of apoptotic-gene expression have provided other possible alternative therapies. Combined effects of cytokines and vitamin derivatives such as retinoic acid (RA) and 1,25 dihydroxyvitamin D3 (VD3) were found more beneficial than any of these agents individually. These agents exhibit cooperative effects, potentiate each other's effects, or both. Therefore, understanding the hematopoietic actions of these agents, their interactions with their receptors, and their differentiation signaling pathways may result in the design of new therapies. However, the role of cytokines in apoptosis is controversial because in some cases they were found to increase tumor cell resistance to apoptosis-inducing agents. Recent studies in the molecular biology of gene regulation, transcription factors, and repressors have led to new possible approaches such as differentiation therapy for the treatment of leukemia. In addition, the development of drugs that act on the molecular level such as imatinib is just the beginning of a new era in molecular targeted therapy in which the drug acts specifically on the leukemic cell. There are many possible combinations of cytokines, retinoids, and VD3, and perhaps the best therapeutic combination is yet to be described. This minireview is an update on the role of cytokines and the therapeutic potential of combinations with agents such as RA, VD3, and other chemotherapeutic agents.
细胞因子网络与平衡对于维持造血功能的正常稳态至关重要。该网络异常可能导致多种血液疾病；然而，其在白血病中的作用尚不清楚。抗肿瘤药物的使用提高了某些类型白血病的生存率，细胞因子辅助治疗可能会有所帮助。化疗方法不再是最佳选择，因为细胞毒性可能会影响正常细胞和白血病细胞，且白血病细胞可能会对化疗药物产生耐药性。诱导分化为成熟表型以及控制凋亡基因表达提供了其他可能的替代疗法。发现细胞因子与维生素衍生物如维甲酸（RA）和1,25-二羟基维生素D3（VD3）的联合作用比这些药物单独使用更有益。这些药物表现出协同作用、相互增强作用或两者兼而有之。因此，了解这些药物的造血作用、它们与受体的相互作用以及它们的分化信号通路可能会带来新疗法的设计。然而，细胞因子在凋亡中的作用存在争议，因为在某些情况下发现它们会增加肿瘤细胞对凋亡诱导剂的耐药性。基因调控、转录因子和阻遏物分子生物学的最新研究带来了新的可能方法，如白血病的分化治疗。此外，作用于分子水平的药物如伊马替尼的开发只是分子靶向治疗新时代的开端，其中药物特异性作用于白血病细胞。细胞因子、类维生素A和VD3有许多可能的组合，也许最佳治疗组合尚未被描述。本综述是关于细胞因子的作用以及与RA、VD3和其他化疗药物等联合治疗潜力的最新进展。
