中国肿瘤生物治疗杂志2017，Vol.24Issue(6)：588-594,7.DOI:10.3872/j.issn.1007-385X.2017.06.003
Twist-1通过MPL促进髓系白血病细胞增殖和耐药
Twist-1 promotes proliferation and drug resistance of myeloid leukemic cells via MPL
摘要
Abstract
Objective:To investigate the correlation between myeloproliferative leukemia virus oncogene (MPL) and Twist-1 in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML),and to explore whether MPL contributes to Twist-l-mediated cell proliferation and drug resistance of leukemia cells.Methods:Bone marrow specimens from 41 patients,who were first diagnosed as AML or CML in Hospital of Blood Diseases Affiliated to Chinese Academy of Medical Sciences between January 2005 and December 2008 (23 cases of AML,18 cases of CML),were selected in this study.Expressions of Twist-1 mRNA and MPL mRNA in hematopoietic tumor cell lines and bone marrow mononuclear cells (BMMCs) of patients with AML or CML were detected by Real-time PCR,and their correlation was analyzed.Lentiviral vector over-expressing MPL (pCDH1-MPL) were constructed and transduced into myeloid leukemia cell lines K562 and U937.Effect of MPL on proliferation,colony formation and drug sensitivity of the leukemic cells were evaluated by cell counting,colony formation assay and MTI assay;in addition,whether Twist-1 promote the proliferation of leukemia cells via MPL was further confirmed.Results:Over-expression of Twist-1 significantly increased the protein expressions of MPL in U937 and K562 cell lines (P ＜ 0.05) while knock-down of Twist-1 significantly decreased the expression of MPL (P ＜0.01).The mRNA expressions of Twist-1 and MPL showed a significant positive correlation in BMMCs of patients with AML and CML (P ＜ 0.05).Over-expression of MPL significantly reduced the drug sensitivity of K562 and U937 cells to daunorubicin and Imatinib (P ＜ 0.01).Enforced expression of MPL in U937 and K562 cells promoted the cell growth and colony formation (all P ＜ 0.01);Twist-1 knockdown with MPL over-expression significantly impaired cell growth and colony formation of leukemia cells (all P ＜ 0.01).Conclusion:Twist-1 promoted proliferation,survival and chemotherapy resistance in the leukemia cells of AML and CML via MPL.关键词
Twist-1基因/MPL基因/髓系白血病/细胞增殖/细胞存活Key words
Twist-1/MPL/myeloid leukemia/cell proliferation/cell survival分类
医药卫生引用本文复制引用
马艳萍,王楠,郭丹,赵杨杨,刘晓燕,尹静,任倩,林永敏,马小彤..Twist-1通过MPL促进髓系白血病细胞增殖和耐药[J].中国肿瘤生物治疗杂志,2017,24(6):588-594,7.基金项目
国家自然科学基金资助项目(No.81670158,No.81470278,No.81600138) （No.81670158,No.81470278,No.81600138）
天津市应用基础与前沿技术研究计划资助项目(青年项目)(No.15JCQNJC10300) （青年项目）
协和青年科研基金滚动资助项目(No.33320140066).Project supported by the National Natural Science Foundation of China(No.81670158,No.81470278,No.81600138),the Youth Program of Applied Basic Research Foundation of Tianjin (No.15JCQNJC10300),and the Science-Technology Foundation for Young Scientists of Chinese Academy of Medical Sciences&Peking Union Medical College (No.33320140066) （No.33320140066）
