Multidrug Resistance Studies in Patients with Acute Myeloid Leukemia

In the bone marrow, a continuous, strictly organized process of blood cell production or hematopoiesis takes place. The human hematopoietic system is capable of replacing the normal daily turnover of blood cells and is capable of maintaining a balance between the blood cell formation and increased blood cell demands such as in bleeding or infection. The different types of cells that are normally present in the peripheral blood are all derived from committed progenitor cells. The comparttnent of these committed progenitor cells is maintained by a small number of pluripotent stem cells. The process of proliferation and differentiation is regulated by cellular interaction, the microenvironment of the bone marrow, several regulatory glycoproteins and hematopoietic growth factors. Leukemia is the condition of malignant transfonnation of hematopoietic cells leading to the accumulation of immature abnonnal cells in blood and bone marrow. According to the clinical presentation, the leukemias are divided in acute and chronic leukemias. Depending on the cell1ineage involved, a further distinction can be made in myeloid and lymphoid leukemias. The focus of this thesis is on "acute myeloid leukemia" (AML). AML is a clonal disease, characterized by a maturation arrest during the differentiation of the hematopoietic cells to mature blood cells, leading to accumulation of a population of immature abnormal myeloid cells, ultimately resulting in suppression of normal hematopoeisis. Clinically, the replacement of normal functional blood cells by leukemic blasts in bone marrow and peripheral blood will result in anemia, granulocytopenia and thrombocytopenia.

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