HIF-1α and GLUT1 gene expression is associated with chemoresistance of acute myeloid leukemia

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-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.