Format

Send to

Choose Destination
Leuk Res. 2018 Oct;73:95-102. doi: 10.1016/j.leukres.2018.09.007. Epub 2018 Sep 18.

Global methylation patterns in primary plasma cell leukemia.

Author information

1
Laboratory of Pre-clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
2
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
3
Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
4
EPIGET LAB, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Unit of Occupational Medicine Fondazione, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
5
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. Electronic address: antonino.neri@unimi.it.
6
Unit of Hematology and Stem Cell Transplantation, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.

Abstract

Primary plasma cell leukemia (pPCL) is a rare and very aggressive variant of multiple myeloma (MM). Specific clinical, biological and molecular patterns distinguish pPCL from MM. Here, we performed a genome-wide methylation analysis by high-density array in 14 newly diagnosed pPCL patients along with 60 MMs, and 5 patients affected by monoclonal gammopathy of uncertain significance (MGUS). Our analysis revealed a global hypomethylation profile associated with pPCL. Additionally, differential methylation patterns were found related to distinct chromosomal aberrations and DIS3 mutations, affecting genes with roles in bone metabolism, cell migration, transcription regulation or DNA damage response. When compared with MM patients, pPCL showed a distinct methylation profile mostly characterized by hypomethylated probes specific for genes involved in several processes like cell adhesion and migration. Furthermore, decreasing methylation levels were evidenced for genes significantly modulated in the progressive phases of plasma cell dyscrasias, from MGUS to MM and pPCL. Overall, our data provide new insights into the molecular characterization of pPCL, thus being potentially useful in the prognostic stratification or identification of novel molecular targets.

KEYWORDS:

Gene expression; Methylation; Microarray profiling; Plasma cell leukemia

PMID:
30257227
DOI:
10.1016/j.leukres.2018.09.007
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center