title: H-ferritin overexpression promotes radiation-induced leukemia/lymphoma in mice.
abstract: H-ferritin (HF) is a core subunit of the iron storage protein ferritin and is related to the pathogenesis of malignant diseases. HF overexpression is present in human hematologic malignancies, suggesting that HF overexpression may contribute to the development of hematologic cancers. However, in vivo evidence that HF is directly linked to hematologic tumorigenesis has not yet been shown. In this study, we show that transgenic (tg) mice overexpressing the human HF gene (hHF-tg) developed aggressive radiation-induced thymic lymphoma/leukemia (TL) compared with wild-type (WT) mice, providing evidence that HF overexpression promotes leukemia/lymphomagenesis. Fractionated X-irradiation of hHF-tg mice caused a higher incidence and earlier onset of TL compared with WT mice. Immunological and pathological features of TLs were similar in both groups. However, proliferative activity of hHF-tg lymphoma cells was higher than that of WT lymphoma cells, and microarray analyses revealed that some leukemia/lymphoma-related genes were differentially expressed in hHF-tg TLs compared with WT TLs. To investigate whether cell damage induced by irradiation is related to leukemia/lymphomagenesis, we evaluated apoptotic levels in the thymus and bone marrow (BM) of hHF-tg and WT groups after fractionated X-irradiation. Apoptosis was augmented in the hHF-tg BM, but not in the thymus, compared with the WT BM, suggesting a possible linkage between increased BM apoptosis by HF overexpression and accelerated radiation-induced TL development. Our findings indicate that HF overexpression is closely related to the development of leukemia/lymphoma, which could have implications for the prevention of malignant hematologic diseases.
authors: Molecular Imaging Center, National Institute of Radiological Sciences,  Chiba 263-8555, Japan.
authors: Sumitaka
authors: S
authors: Hasegawa
authors: Yukie
authors: Y
authors: Morokoshi
authors: Hiroaki
authors: H
authors: Kanda
authors: Satoshi
authors: S
authors: Tsukamoto
authors: Jian
authors: J
authors: Zheng
authors: Atsushi B
authors: AB
authors: Tsuji
authors: Takako
authors: T
authors: Furukawa
authors: Shizuko
authors: S
authors: Kakinuma
authors: Yoshiya
authors: Y
authors: Shimada
authors: Tsuneo
authors: T
authors: Saga
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001052:Apoferritins / Q000502:physiology*; D017209:Apoptosis / Q000528:radiation effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007953:Leukemia, Radiation-Induced / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D008223:Lymphoma / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015996:Survival Rate; D014965:X-Rays / Q000009:adverse effects*
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D001052:Apoferritins; D003849:Deoxyguanosine