Biomedical Engineering Reference
In-Depth Information
Stem Cells in Leukemia and Other Hematological
Malignancies
Mhairi Copland, Alison M. Michie, and Tessa L. Holyoake
Abstract Leukemia was the first malignant condition in which cancer stem
cells were described. Leukemia stem cells (LSCs) have now been described
in a number of different types of leukemia and are currently a major focus
of research interest. LSCs are an important target for treatment of leu-
kemia, and failure to eradicate these very primitive cancer cells is a
common cause of leukemia relapse. Therefore, improved understanding
of the biology of LSCs and the differences between normal hematopoietic
and leukemic stem cells is likely to lead to the development of novel
therapeutic strategies and improvements in leukemia therapy and patient
survival.
Contents
1 Hematopoietic Stem Cells and Normal Hematopoiesis . . . . . . . . . . . . . . . . . . . . .
112
1.1 Early Evidence for the Existence of HSCs . . . . . . . . . . . . . . . . . . . . . . . . . . .
113
1.2 Techniques for Studying Stem Cells in the Hematopoietic System . . . . . . . .
114
2 Leukemia Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
116
2.1 Myeloid Leukemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
116
2.2 Acute Lymphoblastic Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
119
2.3 Candidate LSCs in Chronic Lymphoproliferative Disorders . . . . . . . . . . . . .
119
3 Committed Progenitor Cells as Candidate LSCs . . . . . . . . . . . . . . . . . . . . . . . . . .
120
4 Targeting Self-Renewal in LSC: Potential Therapeutic Strategies . . . . . . . . . . . . .
121
4.1 Wnt Signaling in Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
121
4.2 The Hedgehog Pathway in Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
122
4.3 The Notch Pathway in Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
123
4.4 NF-kB in Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
123
4.5 The HOX Gene Family in Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
123
4.6 The Polycomb Gene BMI-1 in Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . .
124
4.7 The Role of PTEN in Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
124
4.8 Telomerase in Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
125
M. Copland (*)
Faculty of Medicine, University of Glasgow, Glasgow, UK
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