Over-expression of Flt3 induces NF-κB pathway and increases the expression of IL-6

Takahashi, Shinichiro; Harigae, Hideo; Ishii, Keiko Kumura; Inomata, Mitsue; Fujiwara, Tohru; Yokoyama, Hisayuki; Ishizawa, Kenichi; Kameoka, Junichi; Licht, Jonathan D.; Sasaki, Takeshi; Kaku, Mitsuo

doi:10.1016/j.leukres.2005.01.008

« Previous Next »Leukemia Research
Volume 29, Issue 8 , Pages 893-899, August 2005

Over-expression of Flt3 induces NF-κB pathway and increases the expression of IL-6

Shinichiro Takahashi
- Department of Clinical Laboratory Medicine, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan
- Corresponding author. Tel.: +81 22 717 7373; fax: +81 22 717 7390.
Hideo Harigae
- Department of Clinical Laboratory Medicine, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan
Keiko Kumura Ishii
- Department of Clinical Laboratory Medicine, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan
Mitsue Inomata
- Department of Rheumatology and Hematology, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan
Tohru Fujiwara
- Department of Rheumatology and Hematology, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan
Hisayuki Yokoyama
- Department of Rheumatology and Hematology, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan
Kenichi Ishizawa
- Department of Rheumatology and Hematology, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan
Junichi Kameoka
- Department of Rheumatology and Hematology, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan
Jonathan D. Licht
- Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, NY 10029, USA
Takeshi Sasaki
- Department of Rheumatology and Hematology, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan
Mitsuo Kaku
- Department of Clinical Laboratory Medicine, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan

Received 7 January 2005; accepted 7 January 2005. published online 07 March 2011.

Abstract

Activating mutations or over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and other signaling pathways. In this study, we addressed the role of Flt3 in the activation of nuclear factor-kappa B (NF-κB), which is a target molecule of these kinase pathways. In BaF3 cells stably expressing Flt3, a NF-κB-responsive reporter was upregulated and its target gene, IL-6, was increased by the involvement of Flt3-ERK/MAPK-NF-κB pathway. Furthermore, we found a modest positive correlation (r=0.35, p=0.096) between Flt3 and IL-6 mRNA expression in 24 AML specimens. These results suggest a role of Flt3 over-expression in NF-κB pathway.