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Role of Pim1 Gene Overexpression in Pathogenesis of Acute Myeloid Leukemia / 中国实验血液学杂志
Article de Zh | WPRIM | ID: wpr-771901
Bibliothèque responsable: WPRO
ABSTRACT
OBJECTIVE@#To investigate the effect of Pim1 expression up-regulation on cell proliferation, apoptosis, chemotaxis and angiogenesis in acute myeloid leukemia (AML) cell line U937, and to explore the possible molecular mechanism involved, finally to estimate the Pim1 expression in primary AML cells.@*METHODS@#GFP-tagged plasmid for Pim1 overexpression and an empty vector plasmid were constructed, and then a stable Pim1 expressed U937 cell line and a control virus-infected U937 cell line were established by a lentiviral vector system. After confirming Pim1 overexpression in U937 cells, proliferation and apoptosis are determined by CCK-8 Kit and flow cytometry respectively. Transwell chemotaxis assay was used to measure the effect of Pim1 overexpression on AML cells. Flow cytometry and confocal microscopy were applied to detect the influence of Pim1 overexpression on phosphorylated CXCR4 (pCXCR4) and its location. Real-time fluorescence quantitative PCR (qPCR) was used to detect the expression of angiogenesis and adhesion related genes in AML primary cells.@*RESULTS@#The lentivirus-infected AML cell line with Pim1 overex-pression and the control virusinfected AML cell line were established successfully. The Pim1 overexpression could enhance the proliferation and inhibit the cell apoptosis, moreover accompnied with the increasing expression of cyclin D1, phosphorylated BAD (pBAD) and pCXCR4. After SDF-1 α stimuli, Pim1 overexpression induced AML cell chemotaxis accompanied with p-CXCR4 expression and calcium influx increment. Pim1 overexpression has no effect on angiogenesis. Pim1 mRNA expression was significantly higher in AML patients than the healthy people.@*CONCLUSION@#Pim1 plays an important role in the pathogenesis of AML, which not only promotes AML cell proliferation and inhibition of apoptosis, but also enhances the chemotactic ability of leukemia cells, which closely relates with Pim1 phosphorylation of CXCR4 and the increase of intracellular calcium ion influx signals.
Sujet(s)
Texte intégral: 1 Indice: WPRIM Sujet Principal: Leucémie aigüe myéloïde / Transduction du signal / Apoptose / Cellules U937 / Prolifération cellulaire / Protéines proto-oncogènes c-pim-1 / Génétique Type d'étude: Etiology_studies Limites du sujet: Humans langue: Zh Texte intégral: Journal of Experimental Hematology Année: 2019 Type: Article
Texte intégral: 1 Indice: WPRIM Sujet Principal: Leucémie aigüe myéloïde / Transduction du signal / Apoptose / Cellules U937 / Prolifération cellulaire / Protéines proto-oncogènes c-pim-1 / Génétique Type d'étude: Etiology_studies Limites du sujet: Humans langue: Zh Texte intégral: Journal of Experimental Hematology Année: 2019 Type: Article