title: HIF-1α and GLUT1 gene expression is associated with chemoresistance of acute myeloid leukemia.
abstract: OBJECTIVE
  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-1α 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-1α gene expression in an AML cell line and HIF-1α and GLUT1 mRNA expression was measured by real-time quantitative polymerase chain reaction assay (qPCR).
  
  
  RESULTS
  High levels of HIF-1α 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-1α gene.
  
  
  CONCLUSIONS
  Our data revealed that over-expression of HIF-1α and GLUT1 might play a role in the chemoresistance of AML. GLUT1 might be a potential target to reverse such drug resistance.
authors.affiliation: Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, China E-mail : zs_hematology@163.com.
authors.forename: Kui
authors.initials: K
authors.lastname: Song
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Xuan
authors.forename: Gui-Nian
authors.initials: GN
authors.lastname: Huang
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Song
authors.forename: Qi-Fa
authors.initials: QF
authors.lastname: Liu
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000276:immunology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D018922:HL-60 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495677:SLC2A1 protein, human; D004317:Doxorubicin; D005947:Glucose; D005472:Fluorouracil