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Article

PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis

  • Authors:
    • Min Jeong Ryu
    • Jeongsu Han
    • Soo Jeong Kim
    • Min Joung Lee
    • Xianshu Ju
    • Yu Lim Lee
    • Jeong Hwan Son
    • Jianchen Cui
    • Yunseon Jang
    • Woosuk Chung
    • Ik‑Chan Song
    • Gi Ryang Kweon
    • Jun Young Heo
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, College of Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea, Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea, Brain Research Institute, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea, Department of Biochemistry, College of Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea
  • Pages: 2149-2158
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    Published online on: September 12, 2019
       https://doi.org/10.3892/or.2019.7308
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Abstract

Primary refractory acute myeloid leukemia (AML) and early recurrence of leukemic cells are among the most difficult hurdles to overcome in the treatment of AML. Moreover, uncertainties surrounding the molecular mechanism underlying refractory AML pose a challenge when it comes to developing novel therapeutic drugs. However, accumulating evidence suggests a contribution of phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling to the development of refractory AML. To assess PTEN/AKT signaling in AML, two types of AML cell lines were evaluated, namely control HL60 cells and KG1α cells, a refractory AML cell line that is resistant to idarubicin and cytarabine (AraC) treatment. Changes in the expression level of glycolysis‑ and mitochondrial oxidative phosphorylation‑related genes and proteins were evaluated by reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. The mitochondrial oxygen consumption and extracellular acidification rates were measured using an XF24 analyzer. CCK8 assay and Annexin V/PI staining were used to analyze cell viability and cellular apoptosis, respectively. The PTEN protein was found to be depleted, whereas AKT phosphorylation levels were elevated in KG1α cells compared with HL60 cells. These changes were associated with increased expression of glucose transporter 1 and hexokinase 2, and increased lactate production. AKT inhibition decreased the proliferation of KG1α cells and decreased extracellular acidification without affecting HL60 cells. Notably, AKT inhibition increased the susceptibility of KG1α cells to chemotherapy with idarubicin and AraC. Taken together, the findings of the present study indicate that activation of AKT by PTEN deficiency sustains the refractory AML status through enhancement of glycolysis and mitochondrial respiration, effects that may be rescued by inhibiting AKT activity.
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Copy and paste a formatted citation
Spandidos Publications style
Ryu MJ, Han J, Kim SJ, Lee MJ, Ju X, Lee YL, Son JH, Cui J, Jang Y, Chung W, Chung W, et al: PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis. Oncol Rep 42: 2149-2158, 2019.
APA
Ryu, M.J., Han, J., Kim, S.J., Lee, M.J., Ju, X., Lee, Y.L. ... Heo, J.Y. (2019). PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis. Oncology Reports, 42, 2149-2158. https://doi.org/10.3892/or.2019.7308
MLA
Ryu, M. J., Han, J., Kim, S. J., Lee, M. J., Ju, X., Lee, Y. L., Son, J. H., Cui, J., Jang, Y., Chung, W., Song, I., Kweon, G. R., Heo, J. Y."PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis". Oncology Reports 42.5 (2019): 2149-2158.
Chicago
Ryu, M. J., Han, J., Kim, S. J., Lee, M. J., Ju, X., Lee, Y. L., Son, J. H., Cui, J., Jang, Y., Chung, W., Song, I., Kweon, G. R., Heo, J. Y."PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis". Oncology Reports 42, no. 5 (2019): 2149-2158. https://doi.org/10.3892/or.2019.7308
Copy and paste a formatted citation
x
Spandidos Publications style
Ryu MJ, Han J, Kim SJ, Lee MJ, Ju X, Lee YL, Son JH, Cui J, Jang Y, Chung W, Chung W, et al: PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis. Oncol Rep 42: 2149-2158, 2019.
APA
Ryu, M.J., Han, J., Kim, S.J., Lee, M.J., Ju, X., Lee, Y.L. ... Heo, J.Y. (2019). PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis. Oncology Reports, 42, 2149-2158. https://doi.org/10.3892/or.2019.7308
MLA
Ryu, M. J., Han, J., Kim, S. J., Lee, M. J., Ju, X., Lee, Y. L., Son, J. H., Cui, J., Jang, Y., Chung, W., Song, I., Kweon, G. R., Heo, J. Y."PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis". Oncology Reports 42.5 (2019): 2149-2158.
Chicago
Ryu, M. J., Han, J., Kim, S. J., Lee, M. J., Ju, X., Lee, Y. L., Son, J. H., Cui, J., Jang, Y., Chung, W., Song, I., Kweon, G. R., Heo, J. Y."PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis". Oncology Reports 42, no. 5 (2019): 2149-2158. https://doi.org/10.3892/or.2019.7308
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