Studies on Genetic Aberrations in Acute Myeloid Leukemia

Abstract

Hematopoiesis is the formation of blood cellular components. In mammalian embryonic development, the yolk sac and its vasculature are the source of the first blood cells called hematopoietic stem cells (HSCs) from which all blood cells originate. HSCs are produced by the aorta-gonad-mesonephros region, yolk sac and placenta from where they migrate to the fetal liver, where they expand. Hereafter, HSCs transfer to the bone marrow from where they establish the definitive adult hematopoiesis and reside throughout adulthood. HSCs are responsible for foundation of the adult blood differentiation hierarchy and provide continuous hematopoietic cell production. The major characteristic of HSCs is their self-renewal capacity, i.e., they proliferate to give rise to all different types of blood cells, but the pool of stem cells does not become depleted . HSCs are pluripotent. They generate more committed progenitor cells or other stem cells, i.e., common myeloid and lymphoid progenitor cells (CMPs and CLPs respectively) which differentiate and give rise to the progeny belonging to these two lineages of blood cells. While the lymphoid progenitor cells generate B- and T cells as well as natural killer cells, the myeloid progenitor cells produce the other leukocytes, i.e. granulocytes and monocytes/macrophages, as well as red blood cells (erythrocytes) and platelets (Figure 1). The life span of mature blood cells is relatively short and cell production process is continuous, therefore it demands tight regulation by hematopoietic growth factors. The hematopoietic growth factors are a family of cytokines that interact with specific receptors on hematopoietic cells. These molecules like stem cell factor (SCF) or KIT ligand (KIT-L), granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), and macrophage CSF (M-CSF), regulate the functional activation of the specific cells with which they interact. Hematopoietic growth factors are required for the survival, proliferation, and differentiation of hematopoietic progenitors