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


Aims: Much evidence suggests that increased glucose metabolism in tumor cells might contribute to thedevelopment 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 acutemyeloid leukemia (AML).
Methods: Bone marrow samples were obtained from newly diagnosed and relapsedAML (M3 exclusion) cases. RNA interference with short hairpin RNA (shRNA) was used to stably silence GLUT1or HIF-1α gene expression in an AML cell line and HIF-1α and GLUT1 mRNA expression was measured byreal-time quantitative polymerase chain reaction assay (qPCR).
Results: High levels of HIF-1α and GLUT1 wereassociated with poor responsiveness to chemotherapy in AML. Down-regulation of the expression of GLUT1 byRNA interference obviously sensitized drug-resistant HL-60/ADR cells to adriamycin (ADR) in vitro, comparablewith RNA interference for the HIF-1α gene.
Conclusions: Our data revealed that over-expression of HIF-1α andGLUT1 might play a role in the chemoresistance of AML. GLUT1 might be a potential target to reverse suchdrug resistance.