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Molecular Evolution of Leukemia Stem Cells

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Stem Cells Handbook

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Abstract

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.

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Abbreviations

5-LO:

Arachidonate 5-lipoxygenase

AML:

Acute myeloid leukemia

BAD:

Bcl-2-related death promoter

BAK:

Bcl-2 homologous antagonist killer

B-ALL:

B cell acute lymphoblastic leukemia

BAX:

Bcl-2-associated X protein

Bcl-2:

B-cell lymphoma/leukemia-2

BID:

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

CLL:

Chronic lymphocytic leukemia

CML:

Chronic myeloid leukemia

CSC:

Cancer stem cells

CXCR4:

C-X-C chemokine receptor type 4

EVI1:

Ecotropic viral integration site 1

EZH2:

Enhancer of zeste homolog 2

GMP:

Granulocyte-macrophage progenitor

HDAC:

Histone deacetylase

Hh:

Hedgehog

HLF:

Hepatic leukemia factor

HOX:

Homeobox

HSC:

Hematopoietic stem cell

ICN1:

Intracellular NOTCH1

JAK2:

Janus kinase-2

LSC:

Leukemia stem cells

MPN:

Myeloproliferative neoplasm

PcG:

Polycomb group

PRC:

Polycomb repressive complex

RUNX1:

Runt-related transcription factor 1

Shh:

Sonic Hedgehog

SIRT1:

Sirtuin 1

STAT5:

Signal transducer and activator of transcription-5

T-ALL:

T cell acute lymphoblastic leukemia

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Acknowledgements

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

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Authors and Affiliations

  1. Department of Medicine and Sanford Consortium for Regenerative Medicine, Moores Cancer Center, University of California, San Diego, 2880 Torrey Pines Scenic Drive, La Jolla, CA, 92037, USA

    Leslie A. Crews & Catriona H. M. Jamieson M.D., Ph.D.

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  1. Leslie A. Crews
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  2. Catriona H. M. Jamieson M.D., Ph.D.
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Correspondence to Catriona H. M. Jamieson M.D., Ph.D. .

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  1. New York State Health Department Wadsworth Center, Albany, New York, USA

    Stewart Sell

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Crews, L.A., Jamieson, C.H.M. (2013). Molecular Evolution of Leukemia Stem Cells. In: Sell, S. (eds) Stem Cells Handbook. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-7696-2_33

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