Phosphoinositide-dependent kinase 1 regulates leukemia stem cell maintenance in MLL-AF9-induced murine acute myeloid leukemia

Tianyuan Hu, Cong Li, Yingchi Zhang, Le Wang, Luyun Peng, Hui Cheng, Weili Wang, Yajing Chu, Mingjiang Xu, Tao Cheng, Weiping Yuan

Research output: Contribution to journalArticle

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Abstract

Although great efforts have been made to improve available therapies, the mortality rate of acute myeloid leukemia (AML) remains high due to poor treatment response and frequent relapse after chemotherapy. Leukemia stem cells (LSCs) are thought to account for this poor prognosis and relapse. Phosphoinositide-dependent kinase 1 (PDK1) is a critical regulator of the PI3K/Akt pathway and has been shown to be frequently activated in leukemia. However, the role of PDK1 in the regulation of LSCs in AML is still not clear. Using a PDK1 conditional deletion MLL-AF9 murine AML model, we revealed that the deletion of PDK1 prolonged the survival of AML mice by inducing LSC apoptosis. This was accompanied by the increased expression of the pro-apoptotic genes Bax and p53 and the reduced expression of Stat5, which has been shown to be constitutively activated in leukemia. Thus, our findings suggest that PDK1 plays an essential role in maintaining LSCs. Further delineating the function of PDK1 in LSCs may provide a new strategy for the improved treatment of AML relapse.

Original languageEnglish
Pages (from-to)692-698
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume459
Issue number4
DOIs
StatePublished - Apr 17 2015

Fingerprint

1-Phosphatidylinositol 4-Kinase
Phosphatidylinositols
Stem cells
Acute Myeloid Leukemia
Leukemia
Phosphotransferases
Stem Cells
Maintenance
Recurrence
Chemotherapy
Phosphatidylinositol 3-Kinases
p53 Genes
Genes
Apoptosis
Therapeutics
Drug Therapy
Mortality

Keywords

  • PDK1 Akt MLL-AF9 AML LSCs Apoptosis

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Phosphoinositide-dependent kinase 1 regulates leukemia stem cell maintenance in MLL-AF9-induced murine acute myeloid leukemia. / Hu, Tianyuan; Li, Cong; Zhang, Yingchi; Wang, Le; Peng, Luyun; Cheng, Hui; Wang, Weili; Chu, Yajing; Xu, Mingjiang; Cheng, Tao; Yuan, Weiping.

In: Biochemical and Biophysical Research Communications, Vol. 459, No. 4, 17.04.2015, p. 692-698.

Research output: Contribution to journalArticle

Hu, Tianyuan ; Li, Cong ; Zhang, Yingchi ; Wang, Le ; Peng, Luyun ; Cheng, Hui ; Wang, Weili ; Chu, Yajing ; Xu, Mingjiang ; Cheng, Tao ; Yuan, Weiping. / Phosphoinositide-dependent kinase 1 regulates leukemia stem cell maintenance in MLL-AF9-induced murine acute myeloid leukemia. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 459, No. 4. pp. 692-698.
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