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癌/睾丸抗原MAGE-C1/CT7:多发性骨髓瘤治疗的新靶点。

Cancer/Testis Antigen MAGE-C1/CT7: new target for multiple myeloma therapy.

作者信息

de Carvalho Fabricio, Vettore André L, Colleoni Gisele W B

机构信息

Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo, UNIFESP/EPM, Rua Botucatu, 04023-900 Vila Clementino, SP, Brazil.

出版信息

Clin Dev Immunol. 2012;2012:257695. doi: 10.1155/2012/257695. Epub 2012 Mar 11.

Abstract

Cancer/Testis Antigens (CTAs) are a promising class of tumor antigens that have a limited expression in somatic tissues (testis, ovary, fetal, and placental cells). Aberrant expression of CTAs in cancer cells may lead to abnormal chromosome segregation and aneuploidy. CTAs are regulated by epigenetic mechanisms (DNA methylation and acetylation of histones) and are attractive targets for immunotherapy in cancer because the gonads are immune privileged organs and anti-CTA immune response can be tumor-specific. Multiple myeloma (MM) is an incurable hematological malignancy, and several CTAs have been detected in many MM cell lines and patients. Among CTAs expressed in MM we must highlight the MAGE-C1/CT7 located on the X chromosome and expressed specificity in the malignant plasma cells. MAGE-C1/CT7 seems to be related to disease progression and functional studies suggests that this CTA might play a role in cell cycle and mainly in survival of malignant plasma cells, protecting myeloma cells against spontaneous as well as drug-induced apoptosis.

摘要

癌/睾丸抗原(CTA)是一类很有前景的肿瘤抗原,在体细胞组织(睾丸、卵巢、胎儿和胎盘细胞)中表达有限。癌细胞中CTA的异常表达可能导致染色体分离异常和非整倍体。CTA受表观遗传机制(DNA甲基化和组蛋白乙酰化)调控,是癌症免疫治疗的有吸引力的靶点,因为性腺是免疫特权器官,抗CTA免疫反应可以是肿瘤特异性的。多发性骨髓瘤(MM)是一种无法治愈的血液系统恶性肿瘤,在许多MM细胞系和患者中已检测到几种CTA。在MM中表达的CTA中,我们必须特别指出位于X染色体上且在恶性浆细胞中特异性表达的MAGE-C1/CT7。MAGE-C1/CT7似乎与疾病进展有关,功能研究表明,这种CTA可能在细胞周期中发挥作用,主要是在恶性浆细胞的存活中发挥作用,保护骨髓瘤细胞免受自发凋亡以及药物诱导的凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/3310219/bf1c0753d29f/CDI2012-257695.001.jpg

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