Sapienza University, Department of Human Biotechnologies and Hematology, Rome, Italy.
Expert Opin Ther Targets. 2010 Nov;14(11):1157-76. doi: 10.1517/14728222.2010.522570.
The inactive NF-κB-inhibitor of NF-κB (IκB) complex is activated by stimuli including pro-inflammatory cytokines, mitogens, growth factors and stress-inducing agents. The release of NF-κB facilitates its translocation to the nucleus, where it promotes cell survival by initiating transcription of genes encoding stress-response enzymes, cell-adhesion molecules, pro-inflammatory cytokines and anti-apoptotic proteins. NF-κB and associated regulatory factors (IκB kinase subunits and bcl-3) are implicated in hematological and solid tumour malignancies. NF-κB appears to be involved in cell proliferation control, apoptosis control, angiogenesis promotion and possibly regulation of diffusion of metastases. There are several reports that inhibition of NF-κB as a therapeutic target may have a role in tumour cell death or growth inhibition.
We review data about inhibition of NF-κB in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). We describe the molecular mechanisms underlying NF-κB deregulation in these haematological malignancies.
Constitutive activation of NF-κB in the nucleus has been reported in some varieties of MDS/AML. The in vitro and in vivo results of NF-κB inhibition in myeloid malignancies are highlighted.
NF-κB selective inhibitory drugs may be useful, either as single agents or associated with conventional chemotherapy.
NF-κB 抑制剂（IκB）复合物的无活性形式会被包括促炎细胞因子、有丝分裂原、生长因子和应激诱导剂在内的刺激激活。NF-κB 的释放促进了其向细胞核的易位，在细胞核内，通过启动编码应激反应酶、细胞黏附分子、促炎细胞因子和抗凋亡蛋白的基因转录，促进细胞存活。NF-κB 及其相关调节因子（IκB 激酶亚单位和 bcl-3）与血液系统和实体肿瘤恶性肿瘤有关。NF-κB 似乎参与细胞增殖控制、细胞凋亡控制、血管生成促进以及转移扩散的可能调节。有一些报告表明，抑制 NF-κB 作为治疗靶点可能在肿瘤细胞死亡或生长抑制中发挥作用。
我们回顾了 NF-κB 抑制在急性髓性白血病（AML）和骨髓增生异常综合征（MDS）中的数据。我们描述了这些血液恶性肿瘤中 NF-κB 失调的分子机制。
核内 NF-κB 的组成性激活已在某些 MDS/AML 中报道。强调了 NF-κB 抑制在髓样恶性肿瘤中的体内和体外结果。
NF-κB 选择性抑制药物可能有用，无论是作为单一药物还是与常规化疗联合使用。
