Molecular biology of Hodgkin lymphoma.
Molecular biology of Hodgkin lymphoma.
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DOI：
10.1182/asheducation-2009.1.491
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Kuppers, Ralf
中科院分区：
文献类型：
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作者：
Kuppers, Ralf
霍奇金淋巴瘤(HL)起源于成熟的B细胞，分为经典型淋巴瘤和结节淋巴细胞为主的淋巴瘤(NLPHL)。HL在人类B细胞淋巴瘤中是独一无二的，因为淋巴瘤细胞、经典HL中的Hodgkin和Reed-Sternberg(HRS)细胞以及NLPHL中以淋巴细胞为主的(LP)细胞非常罕见，通常占病变组织细胞的0.1%~10%。此外，HRS细胞在失去B细胞典型基因表达模式的程度上是独一无二的。转录因子网络的解除调控在这个重新编程过程中起着关键作用。HRS细胞显示出很强的转录因子NF-kappaB的构造性。多种机制可能有助于这种非调控的激活，包括通过特定的受体和遗传损伤进行信号传递。最近在约40%的经典型HL患者中发现了TNFAIP3抑癌基因的失活突变，该基因编码了一种负调控的核因子-kappaB活性。在大约40%的患者中，HRS细胞潜伏着感染Epstein-Barr病毒，最近证实了该病毒在HL发病机制中的重要作用，特别是在HRS细胞由于破坏性体细胞突变而失去表达B细胞受体的能力的病例中。
Hodgkin lymphoma (HL) is derived from mature B cells and subdivided into classical HL and nodular lymphocyte predominant HL (NLPHL). HL is unique among human B cell lymphomas because of the rarity of the lymphoma cells, the Hodgkin and Reed-Sternberg (HRS) cells in classical HL and the lymphocyte-predominant (LP) cells in NLPHL, which usually account for 0.1% to 10% of the cells in the affected tissues. Moreover, HRS cells are unique in the extent to which they have lost their B cell-typical gene expression pattern. Deregulation of transcription factor networks plays a key role in this reprogramming process. HRS cells show strong constitutive activity of the transcription factor NF-kappaB. Multiple mechanisms likely contribute to this deregulated activation, including signaling through particular receptors and genetic lesions. Inactivating mutations in the TNFAIP3 tumor suppressor gene, encoding a negative regulator of NF-kappaB activity, were recently identified in about 40% of patients with classical HL. HRS cells are latently infected by Epstein-Barr virus in about 40% of patients, and an important role of this virus in HL pathogenesis-in particular for cases in which HRS cells had lost the capacity to express a B-cell receptor due to destructive somatic mutation-was recently substantiated.