title: Gene expression profiling identifies IRF4-associated molecular signatures in hematological malignancies.
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.
authors.affiliation: Center for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America; HIV/HCV Program, James H. Quillen VA Medical Center, Johnson City, Tennessee, United States of America.
authors.forename: Zhi Q
authors.initials: ZQ
authors.lastname: Yao
authors.affiliation: Center for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America; HIV/HCV Program, James H. Quillen VA Medical Center, Johnson City, Tennessee, United States of America.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Moorman
authors.affiliation: Shaun and Lilly International, LLC, Collierville, Tennessee, United States of America.
authors.forename: Yanji
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Center for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Shunbin
authors.initials: S
authors.lastname: Ning
mesh_terms: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics; D045744:Cell Line, Tumor; D019295:Computational Biology; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D060588:LIM Domain Proteins / Q000235:genetics; D017735:Virus Latency; D000099218:Interferon Regulatory Factor-4
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D050835:Interferon Regulatory Factors; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D000099218:Interferon Regulatory Factor-4; C506386:CFLAR protein, human; C403807:LIMD1 protein, human