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Stem Cells and Leukemia

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Stem Cells and Human Diseases

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Abstract

In the last few years, the concepts governing our understanding of cancer have changed. In particular, the point of view that many leukemias are developmentally well-defined and, like in normal hematopoiesis, driven by a relatively small subset of cells called leukemia stem cells (LSCs) has become well-established. Recent studies suggest that defined subsets of LSCs within a tumor are capable of recreating the entire tumor and thus are responsible for relapse/recurrence and metastasis. This subset of “cancer stem cells” has been postulated to possess certain properties akin to those characterized in hematopoietic stem cells such as the capacity to (1) self-renew and to (2) give rise to non-self-renewing or “differentiated” progeny cells that make up the bulk of a tumor. Among the hematopoietic malignancies, acute myeloid leukemia (AML) is the best characterized thus far with respect to “leukemia stem cells” and much data support that the above two properties exist within a relatively rare subpopulation. Related ­studies have also demonstrated that leukemia stem cells are functionally distinct from bulk cells. These subsets are relatively quiescent or slowly cycling, whereas clonogenic progenitors (“differentiated” progeny which cannot self-renew) proliferate rapidly. Current antiproliferative chemotherapy usually affects these dividing progenitors and induces disease relapses as defined by decreased bulk tumor burden. Relapse is not uncommon however, suggesting the quiescent leukemia stem cells are not effectively removed from circulation by existing therapies. Therefore, new therapies that specifically target leukemia stem cells hold great promise for achieving the elusive cure for cancer.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

APL:

Acute promyelocytic leukemia

B-ALL:

B cell acute lymphoblastic leukemia

CLL:

Chronic lymphocytic leukemia

CML:

Chronic myeloid leukemia

CMP:

Common myeloid progenitor

CSC:

Cancer stem cell

GMP:

Granulocyte-macrophage progenitors

HH:

Hedgehog

HIF:

Hypoxia-inducible factor

HSC:

Hematopoietic stem cell

ICN:

Intracellular Notch

LSC:

Leukemia stem cells

MDS:

Myelodysplastic syndromes

MM:

Multiple myeloma

PcG:

Polycomb group

ROS:

Reactive oxygen species

T-ALL:

T cell acute lymphoblastic leukemia

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Acknowledgements

We would like to thank Dr. Andrew P. Weng for supporting us, Melissa Howard for numerous discussions and help in the editing of manuscript, Sonya Lam and Olena Shevchuk for their collaboration and assistance in the lab.

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  1. Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, V5Z 1 L3, Canada

    Vincenzo Giambra & Christopher R. Jenkins

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  1. Vincenzo Giambra
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Correspondence to Vincenzo Giambra .

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  1. , Pharmacology and Toxicology, University of Kansas Medical Center, Rainbow Blvd 3901, Kansas City, 66160, Kansas, USA

    Rakesh Srivastava

  2. , Pathology and Laboratory Medicine, University of Kansas Medical Center, Rainbow Blvd 3901, Kansas City, 66160, Kansas, USA

    Sharmila Shankar

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Giambra, V., Jenkins, C.R. (2012). Stem Cells and Leukemia. In: Srivastava, R., Shankar, S. (eds) Stem Cells and Human Diseases. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2801-1_13

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