The Important Role of STAT3 in Chronic Lymphocytic Leukaemia Biology.
The Important Role of STAT3 in Chronic Lymphocytic Leukaemia Biology.
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DOI：
10.14735/amko202032
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发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
Trbusek, M
中科院分区：
文献类型：
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作者：
Boudny, M;Trbusek, M
背景技术背景：信号转导和转录激活因子（STAT）蛋白是细胞质内的转录因子，传递细胞因子、激素和生长因子的信号。STAT蛋白控制基本的细胞过程，包括存活、增殖和分化。STAT的不适当激活可能有助于细胞转化和白血病发生。大约70%的实体瘤和血液肿瘤表现出异常的STAT 3表达和/或激活，突出了其在肿瘤发生中的重要作用。在几种实体瘤和血液恶性肿瘤中发现了异常的STAT 3激活。重要的是，STAT蛋白的组成性激活已在几种白血病中发现，包括急性髓性白血病、急性早幼粒细胞白血病、急性淋巴母细胞白血病、慢性髓性白血病和慢性淋巴细胞白血病（CLL）。组成性激活的STAT 3在CLL生物学中起重要作用。CLL细胞在S727上具有组成性磷酸化，在K685上具有乙酰化，在Y 705残基上具有瞬时磷酸化。此外，与健康B淋巴细胞相比，CLL细胞中的STAT 3信使RNA表达显著更高。有趣的是，STAT 3抑制被披露为一个重要的副产品的伊鲁替尼治疗CLL patients.Purpose：本综述的目的是描述的后果STAT 3失调CLL细胞。在这里，我们讨论了CLL细胞中STAT 3激活的异常修饰过程，如增殖，凋亡，B细胞受体信号传导，细胞因子分泌，免疫检查点调节，microRNA调节，游离脂肪酸代谢和线粒体中的电子传递链。
BACKGROUND: Signal transducer and activator of transcription (STAT) proteins are cytoplasmic transcription factors that transmit the signal of cytokines, hormones and growth factors. STAT proteins control fundamental cellular processes including survival, proliferation and differentiation. Inappropriate activation of STATs might contribute to cellular transformation and leukaemogenesis. About 70% of all solid and haematological tumours exhibit aberrant STAT3 expression and/or activation, highlighting its essential role in tumourigenesis. Aberrant STAT3 activation has been found in several solid tumours and haematologic malignancies. Importantly, constitutive activation of STAT proteins has been found in several leukaemias including acute myeloid leukaemia, acute promyelocytic leukaemia, acute lymphoblastic leukaemia, chronic myeloid leukaemia and chronic lymphocytic leukaemia (CLL). Constitutively activated STAT3 plays an important role in CLL biology. CLL cells harbour constitutive phosphorylation on S727 and acetylation on K685 and transient phosphorylation on Y705 residues. Moreover, STAT3 messenger RNA expression is significantly higher in CLL cells compared to healthy B-lymphocytes. Interestingly, STAT3 inhibition was disclosed as an important by-product of ibrutinib treatment in CLL patients.PURPOSE: The purpose of this review is to describe the consequences of STAT3 dysregulation in CLL cells. Here, we discuss aberrantly modified processes by STAT3 activation in CLL cells such as proliferation, apoptosis, B cell receptor signalling, cytokine secretion, immune checkpoint regulation, microRNA regulation, free fatty acid metabolism and electron transport chain in the mitochondria.