Biology of Normal and Leukemic Stem Cells

A fundamental problem in cancer research is the identification of the cell type capable of initiating and sustaining the growth of the neoplastic clone in vivo. The key to solving this problem lies on the observation made over 40 years ago that tumours are heterogeneous and thus might be maintained only by a rare subset of cells called cancer stem cells (CSCs). The blood-related cancer leukaemia was the first disease where human CSCs, or leukaemic stem cells (LSCs), were isolated. Leukaemia can now be viewed as aberrant haematopoietic processes initiated by rare LSCs that have maintained or reacquired the capacity for indefinite proliferation through accumulated mutations and/or epigenetic changes. Yet, despite their critical importance, much remains to be learned about the developmental origin of LSC and the mechanisms responsible for their emergence in the course of the disease. This report will review our current knowledge on normal and leukaemic stem cell development.