期刊
ONCOIMMUNOLOGY
卷 7, 期 9, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2018.1468954
关键词
WASp; p53; malignancies; genetic model; immunodeficiency
资金
- Cancer Society
- Olle Engqvist Byggmastare foundation
- Fundacao para a Ciencia e a Tecnologia
- O. E. och Edla Johanssons vetenskapliga stiftelse
- Lars Hierta Memorial Foundation
- Center for Innovative Medicine/CIMED
- Swedish Research Council
- Childhood Cancer Society
- Ake Olsson foundation
- Bergvall Foundation
- King Gustaf V's 80-year Foundation
- Karolinska Institutet
The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of the actin cytoskeleton in hematopoietic cells and mutated in two severe immunodeficiency diseases with high incidence of cancer. Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in WASp and most frequently associated with lymphoreticular tumors of poor prognosis. X-linked neuropenia (XLN) is caused by gain-of-function mutations in WASp and associated with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To understand the role of WASp in tumorigenesis, we bred WASp(+), WASp(-), and WASp-XLN mice onto tumor susceptible p53(+/-) background and sub-lethally irradiated them to enhance tumor development. We followed the cohorts for 24weeks and tumors were characterized by histology and flow cytometry to define the tumor incidence, onset, and cell origin. We found that p53(+/-)WASp(+) mice developed malignancies, including solid tumors and T cell lymphomas with 71.4% of survival 24weeks after irradiation. p53(+/-)WASp(-) mice showed lower survival rate and developed various early onset malignancies. Surprisingly, the p53(+/-)WASp-XLN mice developed malignancy mostly with late onset, which caused delayed mortality in this colony. This study provides evidence for that loss-of-function and gain-of-function mutations in WASp influence tumor incidence and onset.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据