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HIF-1α and GLUT1 Gene Expression is Associated with Chemoresistance of Acute Myeloid Leukemia

  • Song, Kui (Department of Hematology, Nanfang Hospital of Southern Medical University) ;
  • Li, Min (Department of Pharmacy, The First Affiliated Hospital of Jishou University) ;
  • Xu, Xiao-Jun (Department of Hematology, Nanfang Hospital of Southern Medical University) ;
  • Xuan, Li (Department of Hematology, Nanfang Hospital of Southern Medical University) ;
  • Huang, Gui-Nian (Department of Hematology, Zhongshan City People's Hospital) ;
  • Song, Xiao-Ling (Department of Hematology, Nanfang Hospital of Southern Medical University) ;
  • Liu, Qi-Fa (Department of Hematology, Nanfang Hospital of Southern Medical University)
  • Published : 2014.02.28

Abstract

Aims: Much evidence suggests that increased glucose metabolism in tumor cells might contribute to the development of acquired chemoresistance. However, the molecular mechanisms are not fully clear. Therefore, we investigated a possible correlation of mRNA expression of HIF-$1{\alpha}$ and GLUT1 with chemoresistance in acute myeloid leukemia (AML). Methods: Bone marrow samples were obtained from newly diagnosed and relapsed AML (M3 exclusion) cases. RNA interference with short hairpin RNA (shRNA) was used to stably silence GLUT1 or HIF-$1{\alpha}$ gene expression in an AML cell line and HIF-$1{\alpha}$ and GLUT1 mRNA expression was measured by real-time quantitative polymerase chain reaction assay (qPCR). Results: High levels of HIF-$1{\alpha}$ and GLUT1 were associated with poor responsiveness to chemotherapy in AML. Down-regulation of the expression of GLUT1 by RNA interference obviously sensitized drug-resistant HL-60/ADR cells to adriamycin (ADR) in vitro, comparable with RNA interference for the HIF-$1{\alpha}$ gene. Conclusions: Our data revealed that over-expression of HIF-$1{\alpha}$ and GLUT1 might play a role in the chemoresistance of AML. GLUT1 might be a potential target to reverse such drug resistance.

Keywords

GLUT1;HIF-$1{\alpha}$;glucose metabolism;chemoresistance

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