Kupsa Tomas, Horacek Jan Milos, Jebavy Ladislav
Department of Internal Medicine, University of Defence, Faculty of Military Health Sciences in Hradec Kralove, Czech Republic.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012 Dec;156(4):291-301. doi: 10.5507/bp.2012.108. Epub 2012 Dec 7.
Acute myeloid leukemia (AML) shows a high degree of heterogeneity owing to a variety of mutations and the mechanisms of leukemogenesis. This heterogeneity is often not reflected in standard treatment approaches which while providing predictable outcomes in the majority of patients fail in particular cases even with high-dose multiagent chemotherapy regimens. Further, the unselective effect of chemotherapy leads to high treatment-related toxicity and the enormous risk of infection during prolonged pancytopenia, preventing further dose escalation.
Cytokines play a role in leukemogenesis, AML cell persistence and treatment outcome. In this review we highlight cytokine dependent mechanisms essential for AML cell survival and the role of single cytokines in leukemogenesis and allogeneic transplantation-related phenomena. Cytokine-related mechanisms of leukemogenesis, AML cell persistence and resistance to chemotherapy are complex. Modulation of the cytokine network can disrupt signalling pathway activation and overcome the high resistance to treatment. It may also increase the selectivity of AML treatment, reduce the overall treatment-related toxicity and improve outcomes of AML treatment in all age groups of patients.
This review provides a deeper insight into these processes with focus on the most vulnerable step. Special attention is paid to the possibility of selective influence on defined cell populations for therapeutic target. We believe that modulating cytokine-dependent processes in AML is an approach that could be included in standard chemotherapeutic regimens for improving overall treatment outcome.
由于多种突变和白血病发生机制，急性髓系白血病（AML）表现出高度的异质性。这种异质性在标准治疗方法中往往没有得到体现，标准治疗方法虽然能在大多数患者中提供可预测的结果，但在某些特定情况下，即使采用高剂量多药化疗方案也会失败。此外，化疗的非选择性作用会导致高治疗相关毒性以及长期全血细胞减少期间巨大的感染风险，从而阻碍进一步提高剂量。
细胞因子在白血病发生、AML细胞存活及治疗结果中发挥作用。在本综述中，我们重点介绍了AML细胞存活所必需的细胞因子依赖性机制以及单个细胞因子在白血病发生和异基因移植相关现象中的作用。白血病发生、AML细胞存活及化疗耐药的细胞因子相关机制很复杂。调节细胞因子网络可破坏信号通路激活并克服高治疗耐药性。它还可能提高AML治疗的选择性，降低总体治疗相关毒性，并改善所有年龄组AML患者的治疗结果。
本综述更深入地探讨了这些过程，重点关注最脆弱的步骤。特别关注对特定细胞群体进行选择性影响以作为治疗靶点的可能性。我们认为，调节AML中细胞因子依赖性过程是一种可纳入标准化疗方案以改善总体治疗结果的方法。
