[The microenvironment and hematopoiesis]

Successive steps in hematopoietic differentiation occur in the bone marrow in close contact with non hematopoietic components of the microenvironment. The crucial importance of these interactions in the regulation of early hematopoietic events has been convincingly demonstrated in vivo in the mutated steel mouse, and confirmed more recently in vitro in long-term cultures. Parts of the signal mediating these interactions are represented by locally secreted CSF-like growth factors or more recently characterized inhibitors of proliferation. more importantly however appears to be direct cell-cell communication, especially in the regulation of erythropoiesis and recent data suggest that specific adhesion processes might be required initially. As neoplastic clonal dominance is usually not maintained in vitro, experimental evidence for the involvement of the microenvironment in the regulation of leukemic hemopoiesis is still pending. However, it has been shown recently that in some conditions stromal cells may be manipulated in vitro and alter growth properties of leukemic cells. Understanding mechanisms regulating the interactions between hematopoietic and stromal cells may be of considerable importance since it should be possible to delineate and subsequently modulate in vitro the factors affecting stem cell properties. This might lead to alternative therapeutic strategy.