Anticancer Effects of Intermittent Hypoxia in Acute Myeloid Leukemia

  • Guo-Qiang ChenEmail author
  • Wei Liu


Acute myeloid leukemia (AML), a commonly developed heterogenous group of hematopoietic malignancies, is characterized by maturation/differentiation block at specific stages during the hematopoietic development. Recently, we reported that moderate hypoxia and hypoxia-mimetic agents could induce the differentiation of human AML cells in culture. Also, hypoxia-mimetic agents enhance differentiation in acute promyelocytic leukemic cells induced by arsenic trioxide (As2O3). In vivo studies show that intermittent hypoxia significantly prolongs the survival of transplanted leukemic mice with inhibition of infiltration and differentiation induction of leukemic cells. Further investigations explore the role of hypoxia-inducible factor-1alpha (HIF-1α) in differentiation of myeloid leukemic cell, in which HIF-1α physically interact with so as to increase the activities of two critical hematopoietic transcription factors, CCAAT/enhancer binding protein alpha (C/EBPα) and Runt-related transcription protein 1(Runx1), whereas C/EBPα competes with HIF-1β and significantly inhibits the DNA-binding ability of HIF-1. Besides, HIF-1α has been shown to play a part in all-trans retinoic acid (ATRA)-induced differentiation of leukemic cells. Therefore, these observations disclose the two-edged sword effect of hypoxia/HIF-1α. Additional investigations may uncover ways to mimic the differentiative effects of hypoxia in a manner that will benefit human patients with AML.


Acute Myeloid Leukemia U937 Cell Acute Promyelocytic Leukemia Acute Myeloid Leukemia Patient Intermittent Hypoxia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Acute myeloid leukemia


Acute myeloid leukemia-1


Aryl-hydrocarbon receptor nuclear transporter


Arsenic trioxide


All-trans retinoic acid


Bone marrow


CCAAT/enhancer binding protein alpha


Cobalt chloride






Electrophoretic mobility shift assay


Flow cytometry analysis


Hypoxia-inducible factor-1alpha


Hypoxia-responsive element


Hematopoietic stem cells


Interleukin-1 receptor antagonist

LacO array

Lac operator heterochromatic array, Operator (LacO) heterochromatic array


Neutrophil cytosolic factor-1


Oxygen-dependent degradation domain


Prolyl hydroxylases


Promyelocytic leukemia-retinoic acid receptor alpha


PML oncogenic domains


Runt-related transcription protein 1


Short-hairpin RNAs


Secreted phosphoprotein 1


Vascular endothelial growth factor


von Hippel-Lindau


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Copyright information

© Springer-Verlag London 2012

Authors and Affiliations

  1. 1.Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education of ChinaShanghai Jiao Tong University School of MedicineShanghaiChina

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