Sacco Antonio, Fenotti Adriano, Affò Loredana, Bazzana Stefano, Russo Domenico, Presta Marco, Malagola Michele, Anastasia Antonella, Motta Marina, Patterson Christopher J, Rossi Giuseppe, Imberti Luisa, Treon Steven P, Ghobrial Irene M, Roccaro Aldo M
ASST Spedali Civili, Coordinamento e Progettazione Ricerca Clinica, CREA Laboratory, Brescia, BS, Italy.
ASST Spedali Civili, SITRA, Brescia, BS, Italy.
Oncotarget. 2017 May 23;8(21):35435-35444. doi: 10.18632/oncotarget.16130.
The Literature has recently reported on the importance of genomics in the field of hematologic malignancies, including B-cell lymphoproliferative disorders such as Waldenström's Macrolgobulinemia (WM). Particularly, whole exome sequencing has led to the identification of the MYD88L265P and CXCR4C1013G somatic variants in WM, occurring in about 90% and 30% of the patients, respectively. Subsequently, functional studies have demonstrated their functional role in supporting WM pathogenesis and disease progression, both in vitro and in vivo, thus providing the pre-clinical evidences for extremely attractive targets for novel therapeutic interventions in WM. Of note, recent evidences have also approached and defined the transcriptome profiling of WM cells, revealing a signature that mirrors the somatic aberrations demonstrated within the tumor clone. A parallel research field has also reported on microRNAs (miRNAs), highlighting the oncogenic role of miRNA-155 in WM. In the present review, we focus on the latest reports on genomics and miRNAs in WM, providing an overview of the clinical relevance of the latest acquired knowledge about genomics and miRNA aberrations in WM.
最近的文献报道了基因组学在血液系统恶性肿瘤领域的重要性,包括B细胞淋巴增殖性疾病,如华氏巨球蛋白血症(WM)。特别是,全外显子组测序已导致在WM中鉴定出MYD88L265P和CXCR4C1013G体细胞变异,分别发生在约90%和30%的患者中。随后,功能研究已证明它们在体外和体内支持WM发病机制和疾病进展中的功能作用,从而为WM新型治疗干预极具吸引力的靶点提供了临床前证据。值得注意的是,最近的证据也探讨并定义了WM细胞的转录组谱,揭示了一种反映肿瘤克隆内体细胞畸变的特征。一个平行的研究领域也报道了微小RNA(miRNA),强调了miRNA - 155在WM中的致癌作用。在本综述中,我们重点关注WM中基因组学和miRNA的最新报道,概述关于WM中基因组学和miRNA畸变的最新获得知识的临床相关性。