Search

Blood cell formation is governed by the haemopoietic growth factors that control the proliferation, maturation and survival of the haemopoietic progenitor cells via activation of receptors expressed on the cell membrane. Most of these receptors share structural features and have been grouped in the haemopoietin or class I receptor superfamily. Recently considerable progress has been made in elucidating the regions critical for the function of these receptors and the signal transduction mechanisms that they activate. Moreover, it has become clear that certain clinical haematological conditions can be linked to specific defects in these receptors. The significance of defects in the receptor for granulocyte colony-stimulating factor (G-CSF) in the pathogenesis of severe congenital neutropenia and acute myeloid leukaemias is discussed.

Acute leukaemia blast cells fail to mature into terminally differentiated cells and accumulate in the haemopoietic tissues. In analogy with normal haemopoiesis, the leukaemic mass is largely non-dividing and descends from a small pool of leukaemic progenitor cells with high proliferative activity. In vitro culture methods have become powerful instruments to analyse human leukaemia progenitor cells. These techniques have in recent years been considerably improved as the result of the availability of the recombinant HGFs. Here we have summarized the current insights in the growth properties of acute leukaemia progenitor cells, derived from the application of fully defined in vitro assays. We have discussed the proliferation and maturation abilities in relation to cytogenetic abnormalities, status of growth factor receptors and the property of autocrine growth stimulation and evaluated the significance of these findings for the understanding of the pathogenesis of acute myeloblastic leukaemia and acute lymphoblastic leukaemia.

Since their introduction in the early seventies, in vitro culture techniques for human acute leukaemia cells have been modified and improved considerably. Primarily, this is the result of the availability of the recombinant haematopoietic growth factors (HGFs). It is now possible to evaluate HGF responses of acute leukaemia cells in colony and DNA synthesis assays under fully defined conditions. In this chapter we summarize the current insights into the growth properties of human acute leukaemia progenitor cells and evaluate the potential significance of the application of in vitro clonogenic assays for refining the diagnosis of acute leukaemia, for detecting minimal residual disease and for monitoring therapy.