Global methylation patterns in primary plasma cell leukemia

Katia Todoerti, Giovanni Calice, Stefania Trino, Vittorio Simeon, Marta Lionetti, Martina Manzoni, Sonia Fabris, Marzia Barbieri, Alessandra Pompa, Luca Baldini, Valentina Bollati, Pietro Zoppoli, Antonino Neri, Pellegrino Musto

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalLeukemia Research
Volume73
DOIs
Publication statusPublished - Oct 1 2018

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Keywords

  • Gene expression
  • Methylation
  • Microarray profiling
  • Plasma cell leukemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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