RESUMO
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.
Assuntos
Genômica/métodos , MicroRNAs/genética , Fator 88 de Diferenciação Mieloide/genética , Receptores CXCR4/genética , Macroglobulinemia de Waldenstrom/genética , Progressão da Doença , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Mutação , Sequenciamento do Exoma/métodosRESUMO
Epigenomics refers to study of the epigenome, which represents changes in gene expression that are not induced by DNA sequence aberrations. For instance, DNA methylation, histone acetylation and microRNAs may modulate gene expression without altering the gene sequence. Waldenström's macroglobulinaemia (WM) is a low-grade B-cell lymphoma, classified as lymphoplasmacytic lymphoma, characterized by the presence of clonal lymphoplasmacytic cells in the bone marrow and serum monoclonal immunoglobulin-M in the circulation. It is a rare disease and, although indolent, it remains incurable with a median overall survival of 5-6 years. Most patients succumb to disease progression. WM cells present with aberrant histone hypoacetylation that may be explained, at least in part, via deregulated microRNAs, thus suggesting the use of histone deacetylase inhibitors or microRNA-based therapies in this disease.