Molecular Evolution of Leukemia Stem Cells

  • Leslie A. Crews
  • Catriona H. M. Jamieson


Many cancers are propagated by cells that have acquired stem cell properties, including enhanced capacity for self-renewal, survival, aberrant differentiation, and dormancy related to cell migration and retention in supportive niches. Although the majority of cancer treatments eliminate rapidly dividing cells, patients suffering from hematologic malignancies continue to relapse and develop resistance to standard therapies. Initiating oncogenic events has been described at the level of the hematopoietic stem cell in leukemias of both myeloid and lymphoid types. During leukemic progression, this abnormal progenitor cell compartment expands and evolves from a molecular standpoint, resulting in the activation of pro-survival and self-renewal signaling pathways and facilitating the acquisition of additional stem cell-like functional properties. In this chapter we will discuss leukemia stem cells (LSC) evolution at a functional, genetic, and epigenetic level and address the contribution of these molecular alterations to the progression of myeloid and lymphoid leukemias driven by therapeutically recalcitrant LSC.


Acute Myeloid Leukemia Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Cancer Stem Cell Leukemia Stem Cell 
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.



Arachidonate 5-lipoxygenase


Acute myeloid leukemia


Bcl-2-related death promoter


Bcl-2 homologous antagonist killer


B cell acute lymphoblastic leukemia


Bcl-2-associated X protein


B-cell lymphoma/leukemia-2


BCL2-like 11 (BIM) and BH3-interacting domain death agonist


Chronic lymphocytic leukemia


Chronic myeloid leukemia


Cancer stem cells


C-X-C chemokine receptor type 4


Ecotropic viral integration site 1


Enhancer of zeste homolog 2


Granulocyte-macrophage progenitor


Histone deacetylase




Hepatic leukemia factor




Hematopoietic stem cell


Intracellular NOTCH1


Janus kinase-2


Leukemia stem cells


Myeloproliferative neoplasm


Polycomb group


Polycomb repressive complex


Runt-related transcription factor 1


Sonic Hedgehog


Sirtuin 1


Signal transducer and activator of transcription-5


T cell acute lymphoblastic leukemia



The authors wish to thank Jonathan Lee for assistance with figure design and preparation.


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Copyright information

© Springer Science + Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Medicine and Sanford Consortium for Regenerative Medicine, Moores Cancer CenterUniversity of California, San DiegoLa JollaUSA

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