NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells.
NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells.
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DOI：
10.3390/cancers2041838
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发表时间：
2010-11-05
期刊：
影响因子：
5.2
通讯作者：
Fernandes MT
中科院分区：
文献类型：
--
作者：
Dos Santos NR;Ghezzo MN;da Silva RC;Fernandes MT
两个主要的NF-κB信号通路，经典和非经典，在生物体中执行不同的功能已被表征。在淋巴系统恶性肿瘤中，这些NF-κB信号通路的编码基因突变的鉴定证实了它们在白血病发生中的关键作用。T细胞急性淋巴细胞白血病（T-ALL）是一种侵袭性的胸腺细胞恶性肿瘤，尽管治疗取得了重大进展，但仍可能致命。尽管在T-ALL中尚未报道NF-κB基因突变，但在人T-ALL和急性T细胞白血病小鼠模型中观察到NF-κB组成性激活。尽管这些研究揭示了急性T细胞白血病中经典和非经典NF-κB通路成员的激活，但只有抑制经典NF-κB信号传导才能损害白血病T细胞生长。除了在白血病T细胞中发挥重要的促癌作用外，NF-κB信号还通过其在微环境基质细胞中的作用来调节T细胞白血病的发生。本文综述了这些转录因子在T-ALL中的作用的最新数据，并指出进一步的研究对确定NF-κB抑制作为治疗T-ALL的手段的价值至关重要。
Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL.