Candidate genes of Waldenström's macroglobulinemia: current evidence and research.
Candidate genes of Waldenström's macroglobulinemia: current evidence and research.
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DOI：
10.2147/tacg.s42690
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Roccaro A
中科院分区：
文献类型：
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作者：
Bianchi G;Sacco A;Kumar S;Rossi G;Ghobrial I;Roccaro A
华氏巨球蛋白血症 (WM) 是一种相对罕见的惰性恶性肿瘤，由产生免疫球蛋白 M 的 B 细胞引起。世界卫生组织将其归类为淋巴浆细胞淋巴瘤，患者通常表现为贫血、肝脾肿大和弥漫性淋巴结病。从历史上看，该疾病的遗传特征一直受到 WM 细胞相对较低增殖率的阻碍，从而使核型分析变得具有挑战性。荧光原位杂交、基因阵列和全基因组测序等新技术的使用，为建立 WM 病理生理学候选基因和确定潜在的治疗靶点（例如 L265P MYD88）做出了巨大贡献。 microRNA 的发现以及表观遗传学作为癌基因表达和/或抑癌基因沉默的主要调节机制的认识有助于进一步了解 WM 的发病机制。曾被认为与多发性骨髓瘤（一种终末分化、分泌免疫球蛋白的浆细胞的癌症）非常相似，WM 似乎在基因上与其他惰性 B 细胞淋巴瘤（例如慢性淋巴细胞白血病/小细胞淋巴瘤）相似。 WM 和其他 B 细胞恶性肿瘤家族病例的相对高发病率有助于识别高风险候选基因。在这篇综述中，我们重点关注 WM 发病机制中已确定的基因，特别强调核因子 kappa B 信号通路紊乱和表观遗传机制的关键作用。
Waldenström’s macroglobulinemia (WM) is a relatively uncommon, indolent malignancy of immunoglobulin M-producing B cells. The World Health Organization classifies it as a lymphoplasmacytic lymphoma and patients typically present with anemia, hepatosplenomegaly and diffuse lymphadenopathies. Historically, the genetic characterization of the disease has been hampered by the relatively low proliferative rate of WM cells, thus making karyotyping challenging. The use of novel technologies such as fluorescence in situ hybridization, gene array, and whole genome sequencing has contributed greatly to establishing candidate genes in the pathophysiology of WM and to identifying potential treatment targets, such as L265P MYD88. The discovery of microRNAs and the recognition of epigenetics as a major modulatory mechanism of oncogene expression and/or oncosuppressor silencing have aided in further understanding the pathogenesis of WM. Once thought to closely resemble multiple myeloma, a cancer of terminally differentiated, immunoglobulin-secreting plasma cells, WM appears to genetically cluster with other indolent B-cell lymphomas such as chronic lymphocytic leukemia/small cell lymphoma. The relative high incidence of familial cases of WM and other B-cell malignancies has been helpful in identifying high-risk gene candidates. In this review, we focus on the established genes involved in the pathogenesis of WM, with special emphasis on the key role of derangement of the nuclear factor kappa B signaling pathway and epigenetic mechanisms.