The importance of the genomic landscape in Waldenström's Macroglobulinemia for targeted therapeutical interventions

Oncotarget. 2017 May 23;8(21):35435-35444. doi: 10.18632/oncotarget.16130.

Abstract

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.

Keywords: Waldenström’s Macrolobulinemia; genomics.

Publication types

  • Review

MeSH terms

  • Disease Progression
  • Exome Sequencing / methods
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genomics / methods*
  • Humans
  • MicroRNAs / genetics*
  • Mutation
  • Myeloid Differentiation Factor 88 / genetics*
  • Receptors, CXCR4 / genetics*
  • Waldenstrom Macroglobulinemia / genetics*

Substances

  • CXCR4 protein, human
  • MIRN155 microRNA, human
  • MYD88 protein, human
  • MicroRNAs
  • Myeloid Differentiation Factor 88
  • Receptors, CXCR4