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Archive > Volume 24 Issue 6 > 2017,24(6):588-594. DOI:10.3872/j.issn.1007-385X.2017.06.003 Prev Next
Basic Research
Twist1 promotes proliferation and drug resistance of myeloid leukemic cells via MPL
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Abstract:
Objective:To investigate the correlation between myeloproliferative leukemia virus oncogene (MPL) and Twist1 in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), and to explore whether MPL contributes to Twist1mediated 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 Twist1 mRNA and MPL mRNA in hematopoietic tumor cell lines and bone marrow mononuclear cells (BMMCs) of patients with AML or CML were detected by Realtime PCR, and their correlation was analyzed. Lentiviral vector overexpressing MPL (pCDH1MPL) 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 MTT assay; in addition, whether Twist1 promote the proliferation of leukemia cells via MPL was further confirmed. Results: Overexpression of Twist1 significantly increased the protein expressions of MPL in U937 and K562 cell lines (P<0.05) while knockdown of Twist1 significantly decreased the expression of MPL (P<0.01). The mRNA expressions of Twist1 and MPL showed a significant positive correlation in BMMCs of patients with AML and CML (P<0.05). Overexpression 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); Twist1 knockdown with MPL overexpression significantly impaired cell growth and colony formation of leukemia cells (all P<0.01). Conclusion: Twist1 promoted proliferation, survival and chemotherapy resistance in the leukemia cells of AML and CML via MPL.
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Project Supported:
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 ScienceTechnology Foundation for Young Scientists of Chinese Academy of Medical Sciences & Peking Union Medical College（No. 33320140066）
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