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