TY - JOUR
T1 - Jun-regulated genes promote interaction of diffuse large B-cell lymphoma with the microenvironment
AU - Blonska, Marzenna
AU - Zhu, Yifan
AU - Chuang, Hubert H.
AU - You, M. James
AU - Kunkalla, Kranthi
AU - Vega, Francisco
AU - Lin, Xin
N1 - Publisher Copyright:
© 2015 by The American Society of Hematology.
PY - 2015/2/5
Y1 - 2015/2/5
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2014-04-568188
DO - 10.1182/blood-2014-04-568188
M3 - Article
C2 - 25533033
AN - SCOPUS:84922364525
SN - 0006-4971
VL - 125
SP - 981
EP - 991
JO - Blood
JF - Blood
IS - 6
ER -