Live kinase B1 maintains CD34+CD38 AML cell proliferation and self-renewal

  • Huihan Wang
  • Xiaobin Wang
  • Na Xin
  • Lin Qi
  • Aijun Liao
  • Wei Yang
  • Zhuogang Liu
  • Chenghai Zhao
Article

Abstract

Live kinase B1 (LKB1) has been recognized as a tumor suppressor in many human cancers; however, LKB1 maintains self-renewal of hematopoietic stem cells (HSCs). The existence of leukemia stem cells (LSCs) is responsible for drug resistance and leukemia relapse. In acute myeloid leukemia (AML), CD34+CD38 fraction is the most enriched compartment for LSCs. We found that LKB1 was upregulated in CD34+CD38 AML cells. LKB1 downregulation suppressed the long-term proliferation of CD34+CD38 AML cells, induced CD34+CD38 AML cells into G2/M phase, and enhanced the sensitivity of CD34+CD38 AML cells to chemotherapy. Furthermore, LKB1 downregulation in CD34+CD38 AML cells inhibited tumor formation in NOD-SCID mice. Downregulation of LKB1 gene makes LSCs partly loose the characters as stem cells. Gene expression microarray showed that MAPK/ERK pathway was implicated in the regulation of CD34+CD38 AML cell proliferation by LKB1. Together, these findings demonstrate that LKB1 plays an important role in the maintenance of LSCs, which may be responsible for drug resistance and AML relapse.

Keywords

Live kinase B1 Acute myeloid leukemia Leukemia stem cells 

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Huihan Wang
    • 1
  • Xiaobin Wang
    • 3
  • Na Xin
    • 2
  • Lin Qi
    • 4
  • Aijun Liao
    • 1
  • Wei Yang
    • 1
  • Zhuogang Liu
    • 1
  • Chenghai Zhao
    • 2
  1. 1.Department of Hematology, Shengjing HospitalChina Medical UniversityShenyangChina
  2. 2.Department of Pathophysiology, College of Basic Medical ScienceChina Medical UniversityShenyangChina
  3. 3.Department of Urology, Shengjing HospitalChina Medical UniversityShenyangChina
  4. 4.Laboratory of Molecular Neuro-Oncology, Texas Children’s HospitalBaylor College of MedicineHoustonUSA

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