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Molecular Evolution of Leukemia Stem Cells

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

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.

Keywords

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.

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

Notes

Acknowledgements

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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