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Review
. 2015 Jun;6(6):403-12.
doi: 10.1007/s13238-015-0143-7. Epub 2015 Mar 10.

Leukemia stem cells: the root of chronic myeloid leukemia

Hong Zhou  1 , Rongzhen Xu
Affiliations
Review

Leukemia stem cells: the root of chronic myeloid leukemia

Hong Zhou et al. Protein Cell. 2015 Jun.

Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by a chromosome translocation that generates the Bcr-Abl oncogene encoding a constitutive kinase activity. Despite remarkable success in controlling CML at chronic phase by Bcr-Abl tyrosine kinase inhibitors (TKIs), a significant proportion of CML patients treated with TKIs develop drug resistance due to the inability of TKIs to kill leukemia stem cells (LSCs) that are responsible for initiation, drug resistance, and relapse of CML. Therefore, there is an urgent need for more potent and safer therapies against leukemia stem cells for curing CML. A number of LSC-associated targets and corresponding signaling pathways, including CaMKII-γ, a critical molecular switch for co-activating multiple LSC-associated signaling pathways, have been identified over the past decades and various small inhibitors targeting LSC are also under development. Increasing evidence shows that leukemia stem cells are the root of CML and targeting LSC may offer a curable treatment option for CML patients. This review summarizes the molecular biology of LSC and its-associated targets, and the potential clinical application in chronic myeloid leukemia.

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Figures

Figure 1
Figure 1
CaMKII-γ promotes self-renewal of leukemia stem cells via co-activating multiple signaling pathways
Figure 2
Figure 2
Model of different therapies for chronic myeloid leukemia. Hemotherapy kills both leukemia cells and normal hematopoietic stem cells. TKIs selectively kill leukemia cells but not leukemia stem cells. LSC inhibitors selectively kill leukemia stem cells
See this image and copyright information in PMC

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