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Review
. 2014 Sep 26;6(4):473-84.
doi: 10.4252/wjsc.v6.i4.473.

Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

Jianbiao Zhou  1 , Wee-Joo Chng  1
Affiliations
Review

Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

Jianbiao Zhou et al. World J Stem Cells. .

Abstract

Accumulating evidence support the notion that acute myeloid leukemia (AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells (LSC). Similar to their normal counterpart, hematopoietic stem cells (HSC), LSC possess self-renewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normal HSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC.

Keywords: Acute myeloid leukemia; Cancer stem cell; Cell therapy; Immunotherapy; Leukemia stem cell.

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Figures

Figure 1
Figure 1
Diagram of leukemia stem cells, bone marrow microenvironment and phenotypic markers of leukemia stem cell. LSC: Leukemic stem cell.
Figure 2
Figure 2
This illustration shows combination therapies aiming to achieve maximal and synergistic anti-leukemia stem cells effect. HDACi: Histone deacetylase inhibitor; HMTi: Histone methyltransferase inhibitor; BETi: Bromodomain and Extra-Terminal inhibitor; Brd4: Bromodomain-containing protein 4; Ac: acetylation; Me: methylation; NK-cell: Natural killer-cell.
See this image and copyright information in PMC

References

    1. Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, Ritchey JK, Young MA, Lamprecht T, McLellan MD, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481:506–510. - PMC - PubMed
    1. Walter MJ, Shen D, Ding L, Shao J, Koboldt DC, Chen K, Larson DE, McLellan MD, Dooling D, Abbott R, et al. Clonal architecture of secondary acute myeloid leukemia. N Engl J Med. 2012;366:1090–1098. - PMC - PubMed
    1. Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, Koboldt DC, Wartman LD, Lamprecht TL, Liu F, Xia J, et al. The origin and evolution of mutations in acute myeloid leukemia. Cell. 2012;150:264–278. - PMC - PubMed
    1. Brandts CH, Berdel WE, Serve H. Oncogenic signaling in acute myeloid leukemia. Curr Drug Targets. 2007;8:237–246. - PubMed
    1. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–648. - PubMed