PMID- 32341354
OWN - NLM
STAT- MEDLINE
DCOM- 20210331
LR  - 20210427
IS  - 2041-4889 (Electronic)
VI  - 11
IP  - 4
DP  - 2020 Apr 27
TI  - Oxidative resistance of leukemic stem cells and oxidative damage to hematopoietic 
      stem cells under pro-oxidative therapy.
PG  - 291
LID - 10.1038/s41419-020-2488-y [doi]
LID - 291
AB  - Leukemic stem cells (LSCs) and hematopoietic stem cells (HSCs) are both dependent 
      on the hypoxic bone marrow (BM) microenvironment (also known as the BM niche). 
      There is always fierce competition between the two types of cells, and the former 
      exhibits a greater competitive advantage than the latter via multiple mechanisms. 
      Under hypoxia, the dynamic balance between the generation and clearing of 
      intracellular reactive oxygen species (ROS) is conducive to maintaining a 
      quiescent state of cells. Quiescent LSCs can reside well in the BM niche, 
      avoiding attack by chemotherapeutic agents, which is the cause of 
      chemotherapeutic resistance and relapse in leukemia. HSCs acquire energy mainly 
      through anaerobic glycolysis, whereas LSCs achieve energy metabolism largely 
      through mitochondrial oxidative respiration. Mitochondria are the primary site of 
      ROS generation. Thus, in theory, mitochondria-mediated respiration will cause an 
      increase in ROS generation in LSCs and a higher intracellular oxidative stress 
      level. The sensitivity of the cells to pro-oxidant drugs increases as well, which 
      allows for the selective clearing of LSCs by pro-oxidative therapy. However, HSCs 
      are also highly sensitive to changes in ROS levels, and the toxic effects of 
      pro-oxidant drugs on HSCs poses a major challenge to pro-oxidative therapy in 
      leukemia. Given the above facts, we reviewed studies on the oxidative resistance 
      of LSCs and the oxidative damage to HSCs under pro-oxidative therapy. An in-depth 
      investigation into the oxidative stress status and regulatory mechanisms of LSCs 
      and HSCs in hypoxic environments will promote our understanding of the survival 
      strategy employed by LSCs and the mechanism of the oxidative damage to HSCs in 
      the BM niche, thus facilitating individualized treatment of leukemia patients and 
      helping eliminate LSCs without disturbing normal hematopoietic cells.
FAU - Chen, Yongfeng
AU  - Chen Y
AD  - Department of Basic Medical Sciences, Medical College of Taizhou University, 
      Taizhou, 318000, Zhejiang, China. cyfeng@tzc.edu.cn.
FAU - Liang, Yong
AU  - Liang Y
AD  - Department of Basic Medical Sciences, Medical College of Taizhou University, 
      Taizhou, 318000, Zhejiang, China.
FAU - Luo, Xingjing
AU  - Luo X
AD  - Department of Basic Medical Sciences, Medical College of Taizhou University, 
      Taizhou, 318000, Zhejiang, China.
FAU - Hu, Qiongying
AU  - Hu Q
AD  - Department of Basic Medical Sciences, Medical College of Taizhou University, 
      Taizhou, 318000, Zhejiang, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200427
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
SB  - IM
MH  - Cell Differentiation
MH  - Hematopoietic Stem Cells/*metabolism
MH  - Humans
MH  - Leukemia/*genetics/pathology
MH  - Oxidative Stress/*genetics
MH  - Tumor Microenvironment
PMC - PMC7184730
COIS- The authors declare that they have no competing interests.
EDAT- 2020/04/29 06:00
MHDA- 2021/04/01 06:00
PMCR- 2020/04/27
CRDT- 2020/04/29 06:00
PHST- 2019/11/15 00:00 [received]
PHST- 2020/04/08 00:00 [accepted]
PHST- 2020/04/08 00:00 [revised]
PHST- 2020/04/29 06:00 [entrez]
PHST- 2020/04/29 06:00 [pubmed]
PHST- 2021/04/01 06:00 [medline]
PHST- 2020/04/27 00:00 [pmc-release]
AID - 10.1038/s41419-020-2488-y [pii]
AID - 2488 [pii]
AID - 10.1038/s41419-020-2488-y [doi]
PST - epublish
SO  - Cell Death Dis. 2020 Apr 27;11(4):291. doi: 10.1038/s41419-020-2488-y.