Jun-regulated genes promote interaction of diffuse large B-cell lymphoma with the microenvironment

Marzenna Blonska, Yifan Zhu, Hubert H. Chuang, M. James You, Kranthi Kunkalla, Francisco Vega, Xin Lin

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Diffuse large B-cell lymphoma (DLBCL) is anaggressive disease witha high proliferation rate. However, the molecular and genetic features that drive the aggressive clinical behavior of DLBCL are not fully defined. Here, we have demonstrated that activated Jun signaling is a frequent event in DLBCL that promotes dissemination of malignant cells. Downregulation of Jun dramatically reduces lymphoma cell adhesion to extracellular matrix proteins, subcutaneous tumor size in nude mice, and invasive behavior, including bone marrow infiltration and interaction with bone marrow stromal cells. Furthermore, using a combination of RNA interference and gene expression profiling, we identified Jun target genes that are associated with disseminated lymphoma. Among them, ITGAV, FoxC1, and CX3CR1 are significantly enriched in patients with 2 or more extranodal sites. Our results point to activated Jun signaling as a major driver of the aggressive phenotype of DLBCL.

Original languageEnglish (US)
Pages (from-to)981-991
Number of pages11
JournalBlood
Volume125
Issue number6
DOIs
StatePublished - Feb 5 2015

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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