Blastic leukaemias (AML): a biologist's view.

Acute myeloblastic leukaemia is characterised by the extreme clonal proliferation of haematopoietic precursor cells with abnormal or arrested differentiation. Chemotherapy of acute leukaemia is channelled towards the reduction and eradication of leukaemic cells. However, relapse is generally assumed to occur in residual host cells, which are refractory to or elude therapy. The cancer stem cell hypothesis has gained considerable importance in recent years and could interpret this behaviour. This persuasive theory states that cells within a tumour are organised in a hierarchy similar to that of normal tissues and are maintained by a small subset of cells responsible for tumour dormancy. These cells, defined as 'tumour initiating cells' (TICs), possess several properties of normal tissue stem cells. Recently, the TICs associated with AML have been shown to comprise distinct, hierarchically arranged classes similar to those observed for haematopoietic stem cells. We know now that the growth and survival of blasts in AML are driven by the same growth factors that stimulate normal cells. Furthermore, direct evidence of the role of membrane stem cell factor and its receptor c-Kit in cell-cell interactions and cell survival in primary AML blasts have been provided, defining the importance of juxtacrine stimulation. Inhibition of c-Kit signalling induces combinations of cell death: autophagy (compensatory mechanism towards survival) and apoptosis. While recent work confirmed that c-Kit inhibitors reduce cancer cell proliferation, it also demonstrated that future inappropriate prescriptions could cause normal tissue deterioration. The purpose of this paper was to review some of the salient features of leukaemic blasts in support of the proposal that research into neoplasia be increased. Rather than presenting the details of various studies, I have attempted to indicate general areas in which work has been done or is in progress. It is hoped that this survey of the subject will demonstrate a variety of opportunities for additional research in human neoplasia.