| Title | ADAM28 promotes tumor growth and dissemination of acute myeloid leukemia through IGFBP-3 degradation and IGF-I-induced cell proliferation |
| Authors | Zhang, Jia-Min Wang, Chen-Cong Zhang, Gao-Chao Jiang, Qian Yang, Shen-Miao Fu, Hai-Xia Wang, Qian-Ming Zhu, Xiao-Lu Zhu, Hong -Hu Jiang, Hao Wang, Yu Lv, Meng Lu, Jin Chen, Huan Han, Wei Chang, Ying-Jun Kong, Yuan Xu, Lan-Ping Liu, Kai-Yan Huang, Xiao-Jun Zhang, Xiao-Hui |
| Affiliation | Peking Univ, Peoples Hosp, Inst Hematol, 11 Xizhimen South St, Beijing, Peoples R China Beijing Key Lab Hematopoiet Stern Cell Transplant, Beijing, Peoples R China Peking Univ, Collaborat Innovat Ctr Hematol, Beijing, Peoples R China |
| Keywords | Acute myeloid leukemia ADAM28 Prognosis Migration IGF pathway |
| Issue Date | 2019 |
| Publisher | CANCER LETTERS |
| Abstract | ADAM28 has been shown to relate with tumor proliferation and prognosis. The expression of ADAM28 is up regulated in acute myeloid leukemia (AML). However, the mechanism by which ADAM28 regulates the leukemic cell and the prognostic relevance with AML remain unknown. Here, we found that the expression level of ADAM28 was significantly elevated in AML patients suffering a relapse compared with those remaining in complete remission (CR). ADAM28 promoted the proliferation, migration and invasion in leukemic cells in vitro. Additionally, the increased expression of ADAM28 led to more IGFBP-3 degradation and IGF-I-induced cell proliferation. In a xenotransplantation mouse model, knockout of ADAM28 alleviated HL-60 cells growth and dissemination. The cumulative incidence of relapse (CIR) was significantly higher in patients with high ADAM28 expression. When separately considering the impact of ADAM28 on prognosis within the risk stratifications, patients with high ADAM28 expression levels had a significantly higher CIR in the favorable and intermediate risk group but not in poor-risk group. Taken together, these data suggest a pivotal role for ADAM28 in regulating the proliferation and invasion of leukemic cells and in the prediction of relapse in AML patients. |
| URI | http://hdl.handle.net/20.500.11897/552201 |
| ISSN | 0304-3835 |
| DOI | 10.1016/j.canlet.2018.10.028 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 人民医院 |
