The myelodysplastic syndrome: in vitro growth characteristics of hemopoietic progenitor cells.

Blood cell formation results from the continuous proliferation, differentiation and maturation of pluripotent hemopoietic stem cells located in the human bone marrow. In vitro culture assays, developed in the last twenty years, have enabled the identification of the various pluripotent and committed progenitor cells present in human bone marrow by their capacity to form colonies of mature blood cells in vitro. Colony formation dependens on the presence of hemopoietic growth factors in the culture medium, which have become known as the colony stimulating factors (CSFs). At present a number of CSFs can be produced on a large scale through recombinant DNA technology and their biological activities have subsequently been defined. In chapter 1.1 and 1.2 the general principles of hemopoiesis are introduced, i.e., the different models of stem cell renewal and commitment, the various in vitro clonogenic assays for normal as well as for leukemic colony forming cells and the effects of the CSF on progenitor cells and mature blood cells. The myelodysplastic syndrome (MDS) comprises a group of acquired disorders, which are characterized by an ineffective hemopoiesis resulting in cytopenia of one or more cell lineages. Cytogenetic and G-6-PD studies have demonstrated that MDS is a clonal disease of the hemopoietic stem celL The results of some studies suggest that normal hemopoiesis is replaced by the abnormal clone already in an early stage of the disease. Up to fourty percent of the MDS patients eventually develop an acute myeloblastic leukemia. The preleukemic nature of the MDS makes this syndrome of particular interest in the study of leukemogenesis. In chapter 1.3 the clinical, morphological and in vitro growth characteristics of the MDS are introduced.