Acute myeloid leukemia (AML) is characterized by bone marrow accumulation of immature leukemic blast cells. Conventional AML treatment includes induction chemotherapy to achieve disease control, followed by consolidation therapy with conventional chemotherapy or allogeneic/autologous stem cell transplantation (allo/auto-SCT) to eradicate residual disease. Even younger patients receiving the most intensive treatment have a median, long-term, AML-free survival of only 45-50%, highlighting the need for new treatment strategies. The important role of the bone marrow cytokine network during disease development and treatment is suggested by several observations, including: (i) the increased microvascular density (MVD) in leukemic bone marrow, (ii) experimental evidence of cytokine-mediated crosstalk between leukemic and microvascular endothelial cells, (iii) the prognostic impact of angioregulatory cytokine levels both in patients receiving conventional chemotherapy and allo-SCT, and (iv) the experimental evidence for an antileukemic effect of cytokine inhibition in human AML. Several cytokines are constitutively released by human AML cells, including interleukins, chemokines, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and angiopoietins. However, the cytokine system constitutes a functional, interacting network, and recent evidence suggests that analysis of serum cytokine profiles rather than the analysis of single cytokines should be used for prognostic evaluation of AML patients. We will discuss the role of angioregulatory cytokines in leukemogenesis, including their direct effects on the leukemic cells, as well as their indirect contribution to leukemogenesis through angioregulation and crosstalk between leukemic and neighboring stromal cells. We shall also discuss the possibility of targeting angioregulatory cytokines as a part of the treatment strategy in leukemia.

中文翻译：

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人类急性髓细胞性白血病中的血管调节性细胞因子网络-从通过缓解诱导的白血病生成到干细胞移植。

急性髓细胞性白血病（AML）的特征是未成熟白血病母细胞的骨髓积累。常规AML治疗包括诱导化疗以实现疾病控制，然后进行常规化疗的巩固疗法或同种异体/自体干细胞移植（allo / auto-SCT）以根除残留的疾病。即使是接受最深入治疗的年轻患者，中长期，无AML生存率也仅为45-50％，这凸显了对新治疗策略的需求。多项观察结果提示了骨髓细胞因子网络在疾病发展和治疗中的重要作用，其中包括：（i）白血病骨髓中微血管密度（MVD）的升高，（ii）细胞因子介导的白血病与白血病之间的串扰的实验证据。微血管内皮细胞 （iii）血管调节细胞因子水平对接受常规化疗和异源SCT的患者的预后影响，以及（iv）细胞因子抑制对人AML的抗白血病作用的实验证据。人AML细胞组成性释放几种细胞因子，包括白介素，趋化因子，血管内皮生长因子（VEGF），肝细胞生长因子（HGF）和血管生成素。然而，细胞因子系统构成了一个功能性的相互作用网络，最近的证据表明，应使用血清细胞因子谱分析而不是单一细胞因子分析来评估AML患者的预后。我们将讨论血管调节细胞因子在白血病发生中的作用，包括它们对白血病细胞的直接作用，以及它们通过血管调节和白血病细胞与邻近基质细胞之间的串扰对白血病发生的间接贡献。我们还将讨论靶向血管调节性细胞因子作为白血病治疗策略的一部分的可能性。