1. ¹Division of Cell and Molecular Biology, University Health Network, Toronto, Ontario, Canada
2. ²Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada
3. ³Department of Medicine, Laval University, Québec, Canada
4. ⁴Department of Hematology, Enfant-Jésus Hospital, Québec, Canada
5. ⁵Research Center in Infectious Diseases, CHUQ-CHUL, Laval University, Québec, Canada

Correspondence: Dr F Barabé, Research Center in Infectious Diseases, CHUQ-CHUL, Laval University, 2705 boul Laurier, RC-709, Québec, Canada G1V 4G2. E-mail: frederic.barabe@crchul.ulaval.ca

Received 20 April 2008; Revised 16 June 2008; Accepted 4 July 2008; Published online 7 August 2008.

Abstract

The hematopoietic system produces appropriate levels of blood cells over an individual's lifetime through a careful balance of differentiation, proliferation and self-renewal. The acquisition of genetic and epigenetic alterations leads to deregulation of these processes and the development of acute leukemias. A prerequisite to targeted therapies directed against these malignancies is a thorough understanding of the processes that subvert the normal developmental program of the hematopoietic system. This involves identifying the molecular lesions responsible for malignant transformation, their mechanisms of action and the cell type(s) in which they occur. Over the last 3 decades, significant progress has been made through the identification of recurrent genetic alterations and translocations in leukemic blast populations, and their subsequent functional characterization in cell lines and/or mouse models. Recently, primary human hematopoietic cells have emerged as a complementary means to characterize leukemic oncogenes. This approach enables the process of leukemogenesis to be precisely modeled in the appropriate cellular context: from primary human hematopoietic cells to leukemic stem cells capable of initiating disease in vivo. Here we review the model systems used to study leukemogenesis, and focus particularly on recent advances provided by in vitro and in vivo studies with primary human hematopoietic cells.