Open AccessPossible Involvement of Interferon Regulatory Factor 4 (IRF4) in a Clinical Subtype of Adult T‐Cell Leukemia
Author(s) -
Imaizumi Yoshitaka,
Kohno Tomoko,
Yamada Yasuaki,
Ikeda Shuichi,
Tanaka Yuetsu,
Tomonaga Masao,
Matsuyama Toshifumi
Publication year - 2001
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2001.tb02151.x
Subject(s) - irf4 , interferon regulatory factors , biology , peripheral blood mononuclear cell , cell cycle , cancer research , immunology , leukemia , transcription factor , cell , immune system , innate immune system , in vitro , gene , genetics
Interferon regulatory factor (IRF) 4 is the lymphoid‐specific transcription factor that is required for the proliferation of mitogen‐activated T cells. IRF4 has been suggested to be involved in tuniorigenesis because the overexpression of IRF4 caused the transformation of Rat‐1 fibroblasts in vitro. Here, we show that IRF4 is constitutively expressed in adult T‐cell leukemia (ATL)‐derived cell lines, which were infected with human T‐cell leukemia virus type‐I, but hardly expressed the trans‐activator protein, Tax. Similarly, constitutive expression of IRF4 was demonstrated in freshly isolated peripheral blood mononuclear cells (PBMC) from patients with either acute or chronic ATL. However, the high‐level expression of IRF4 was specifically associated with acute ATL. With mitogen‐activated PBMC from healthy donors, cell cycle analyses revealed that the induction of IRF4 occurred prior to cell cycle progression and the cells that had entered the cell cycle were predominantly IRF4‐positive cells. In addition, ectopic expression of IRF4 in Rat‐1 fibroblasts increased the S and G2/M phase population significantly. Taken together, our results indicate that IRF4 is involved in the pathogenesis of ATL through its positive effect on the cell cycle, and that IRF4 can be used as a molecular marker of clinical subtype in ATL.