Immunophenotype definition of the stem/ progenitor cell compartment. Implications for the identification of blast cells in acute leukemia

The defining characteristic of a stem cell is its capacity for extensive self-renewal and retention of multilineage differentiation potential (Gordon, 1993). The complex series of events required to guarantee self-renewal, proliferation and differ-entiation leads to the concept that the stem cell compartment has to be very heterogeneous and hierarchical (Ogawa, 1993). The transition from the primitive quiescent stem cell to the active functional hemopoietic cell requires various in-termediate stages characterised by the progres-sive loss of the self-renewal capacity and pro-gressive lineage restriction and commitment (Williams, 1993). This complex system is main-tained through the action of several regulatory molecules and signals originating from the he-mopoietic microenviroment. Up to now, a large number of growth factors, interleukins, and in-hibitory proteins have been identified, and their role in the regulation of the differentiation and proliferation processes have been extensively verified by many authors (Moore, 1991; Metcalf, 1993). Several positive signals for proliferation and differentiation of stem/progenitor cells have been so far recognised, including the family of colony stimulating factors -CSF (GM-CSF, G-CSF, M-CSF, fibroblast-CSF, Meg-CSF, erythropoietin), interleukins (IL-1, IL-3, IL-6, IL-11, IL-12), and related molecules (Kit-ligand etc.) (Pistoia, 1992). However, the non proliferating state may be seen either as a passive process involving ab-sence of positive signals or an active process in-volving suppressive negative regulators that act as blocking, down modulating, or reducing the function of receptors for positive regulators on stem cells. Negative regulators may also inter-fere with signal transduction pathways, transcrip-tional factors, and mRNA production or stabil-ity, through the interaction with genes activated by positive regulators. They also act indirectly by blocking the synthesis of positive regulators. Some of these hemopoietic factors, such as TGF13 (transforming growth factor), TNFa (tumor necrosis factor), IFNs (interferons), and MIP (macrophage inflammatory protein) display pleiotropic activities.