Gene expression profiling identifies IRF4-associated molecular signatures in hematological malignancies

PLoS One. 2014 Sep 10;9(9):e106788. doi: 10.1371/journal.pone.0106788. eCollection 2014.

Abstract

The lymphocyte-specific transcription factor Interferon (IFN) Regulatory Factor 4 (IRF4) is implicated in certain types of lymphoid and myeloid malignancies. However, the molecular mechanisms underlying its interactions with these malignancies are largely unknown. In this study, we have first profiled molecular signatures associated with IRF4 expression in associated cancers, by analyzing existing gene expression profiling datasets. Our results show that IRF4 is overexpressed in melanoma, in addition to previously reported contexts including leukemia, myeloma, and lymphoma, and that IRF4 is associated with a unique gene expression pattern in each context. A pool of important genes involved in B-cell development, oncogenesis, cell cycle regulation, and cell death including BATF, LIMD1, CFLAR, PIM2, and CCND2 are common signatures associated with IRF4 in non-Hodgkin B cell lymphomas. We confirmed the correlation of IRF4 with LIMD1 and CFLAR in a panel of cell lines derived from lymphomas. Moreover, we profiled the IRF4 transcriptome in the context of EBV latent infection, and confirmed several genes including IFI27, IFI44, GBP1, and ARHGAP18, as well as CFLAR as novel targets for IRF4. These results provide valuable information for understanding the IRF4 regulatory network, and improve our knowledge of the unique roles of IRF4 in different hematological malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CASP8 and FADD-Like Apoptosis Regulating Protein / genetics
  • Cell Line, Tumor
  • Computational Biology
  • Databases, Genetic
  • Gene Expression Profiling*
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / metabolism*
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / virology
  • Herpesvirus 4, Human / physiology
  • Humans
  • Interferon Regulatory Factors / metabolism*
  • Intracellular Signaling Peptides and Proteins / genetics
  • LIM Domain Proteins / genetics
  • Virus Latency

Substances

  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Interferon Regulatory Factors
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • LIMD1 protein, human
  • interferon regulatory factor-4

Grants and funding

This work is supported by the American Society of Hematology Scholar Award to SN (http://www.hematology.org/Awards/Career-Training/463.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.