Clonality studies in myelodysplasia and acute myeloid leukemia

In adult humans, the production of blood cells or hematopoiesis is mainly restricted to the bone marrow. A small number of pluripotent stem cells, which are capable of selfrenewal, can generate committed progenitor cells. The latter are ineversibly committed to the granulocytic, monocytic, erythroid, megakaryocytic or the lymphoid cell lineage. After proliferation and differentiation, the mature blood cells entcr the circulation. The granulocytic and monocytic cells may be designated as myeloid cells; the erythroid cells are sometimes also included in this group. The blood cell formation is regulated by hematopoietic growth factors and cellular interactions e.g. with bone marrow stromal cells. Malignant transformation of hematopoietic cells results in ineffective hematopoiesis. Progenitor and/or precursor cells may accumulate due to a maturation arrest. Depending on the cell lineage involved, these disorders are refelTed to as myeIodysplastic syndrome, acute myeloid or lymphoblastic leukemia, myeloproliferative or lymphoproIiferative disease. The myelodyspIastic syndrome and acute myeloid leukemia are the subjects of investigation of this thesis.