Identification and Modulation of Drug Resistance in Acute Myeloid Leukemia

A continuous, strictly organised process of blood cell production or hematopoiesis normally takes place in the bone marrow. The human hematopoietic system is capable of replacing the normal daily loss of peripheral blood cells, and will adapt the blood cell formation to increased demands such as bleeding or infection. This system is capable of maintaining a balance between cell loss and formation. The different types of blood cells that are normally present in the peripheral blood, are derived from committed progenitor cells. The compartment of these committed progenitor cells is maintained by a small population of pluripotent stem cells. Besides the ability of the stem cells to give rise to committed progenitor cells, they are capable of self-renewal. The process of proliferation and differentiation is regulated by cellular interaction, i.e. the microenvironment in the bone marrow, and several regulatory glycoproteins, the hematopoietic growth factors (HGPs). Malignant transformation of hematopoietic cells somewhere during their development and leading to the accumulation of immature hemopoietic cells is referred to as leukemia. According to the clinical presentation, the leukemias are divided in acute and chronic leukemias. Acute leukemias, if untreated, will lead to death within several weeks or months, while patients with untreated chronic leukemias often may survive for several years. Depending on the cell lineages involved, a further distinction in myeloid or lymphoid leukemias can be made. In this thesis, acute myeloid leukemia is subject of investigation.

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