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

Antonio Sacco, Adriano Fenotti, Loredana Affò, Stefano Bazzana, Domenico Russo, Marco Presta, Michele Malagola, Antonella Anastasia, Marina Motta, Christopher J. Patterson, Giuseppe Rossi, Luisa Imberti, Steven P. Treon, Irene M. Ghobrial and Aldo M. Roccaro _

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Oncotarget. 2017; 8:35435-35444. https://doi.org/10.18632/oncotarget.16130

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Antonio Sacco1, Adriano Fenotti2, Loredana Affò2, Stefano Bazzana3, Domenico Russo4, Marco Presta5, Michele Malagola4, Antonella Anastasia6, Marina Motta6, Christopher J. Patterson7, Giuseppe Rossi6, Luisa Imberti1, Steven P. Treon7, Irene M. Ghobrial7 and Aldo M. Roccaro1

1 ASST Spedali Civili, Coordinamento e Progettazione Ricerca Clinica, CREA Laboratory, Brescia, BS, Italy

2 ASST Spedali Civili, SITRA, Brescia, BS, Italy

3 ASST Spedali Civili, Collegio IPASVI, Brescia, BS, Italy

4 University of Brescia Medical School, Adult Bone Marrow Transplantation Unit, Brescia, BS, Italy

5 University of Brescia Medical School, Dept. of Molecular and Translational Medicine, Brescia, BS, Italy

6 ASST Spedali Civili, Dept. of Hematology, Brescia, BS, Italy

7 Dana-Farber Cancer Institute, Dept. Medical Oncology, Harvard Medical School, Boston, MA, USA

Correspondence to:

Aldo M. Roccaro, email:

Keywords: Waldenström’s Macrolobulinemia, genomics

Received: November 17, 2016 Accepted: February 20, 2017 Published: March 11, 2017


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.

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