Concepts of human leukemic development

Two fundamental problems in cancer research are identification of the normal cell within which cancer initiates and identification of the cell type capable of sustaining the growth of the

neoplastic clone. There is overwhelming evidence that virtually all cancers are clonal and represent the progeny of a single cell. What is less clear for most cancers is which cells within

the tumor clone possess tumorigenic or ‘cancer stem cell’ (CSC) properties and are capable of maintaining tumor growth. The concept that only a subpopulation of rare CSC is responsible for

maintenance of the neoplasm emerged nearly 50 years ago. Testing of this hypothesis is most advanced for the hematopoietic system due to the establishment of functional in vitro and in vivo

assays for stem and progenitor cells at all stages of development. This body of work led to conclusive proof for CSC with the identification and purification of leukemic stem cells capable

of repopulating NOD/SCID mice. This review will focus on the historical development of the CSC hypothesis, the mechanisms necessary to subvert normal developmental programs, and the

identification of the cell in which these leukemogenic events first occur.

This work was supported by the National Cancer Institute of Canada (NCIC) with funds from the Canadian Cancer Society, Canadian Institutes for Health Research, Stem Cell Network of the

National Centres of Excellence, Canadian Genetic Diseases Network of the National Centres of Excellence, and a Canada Research Chair.

Division of Cell and Molecular Biology, University Health Network and Department of Molecular Genetics and Microbiology, University of Toronto, 620 University Ave, Toronto, M5G 2C1, ON,

Canada

Jennifer K Warner, Jean C Y Wang, Kristin J Hope, Liqing Jin & John E Dick

Anyone you share the following link with will be able to read this content: