2013-01-18
Genome-Wide Analysis of Severe Congenital Neutropenia and Leukemia Implications for leukemogenesis
Publication
Publication
Genoombrede analyse van ernstige congenitale neutropenie en leukemie: Implicaties voor leukemogenese
The process of blood cell formation is known as hematopoiesis. During this process mature blood cells are formed in the bone marrow, followed by their release in the peripheral blood. Once in the periphery, mature blood cells exert their functions; erythrocytes play a crucial role in gas transport from the lungs to the peripheral organs and vice versa, platelets are essential for blood clotting and leukocytes, comprising granulocytes, monocytes/macrophages, lymphocytes and natural killer cells, are indispensable for the defense against micro-organisms. The mammalian blood system is self renewing and the number of blood cells is controlled by a tight balance of production and degradation. Throughout the entire life, mature blood cells derive from a small population of pluripotent hematopoietic stem cells (HSCs) within the bone marrow. HSCs have the exceptional ability to and self-renew and differentiate into progenitors of all hematopoietic lineages1. In this way, HSCs provide an unlimited source of blood cells. Hematopoietic progenitors on their turn develop through a number of differentiation stages into mature blood cells (Figure 1). The lifespan of mature blood cells is limited, consequently a constant production is necessary to maintain adequate blood cell numbers2. Hematopoiesis is largely controlled by external signals, e.g., hematopoietic growth factors and cell-cell interactions, within the bone marrow niche2, 3. These are essential for the production of sufficient numbers of blood cells under physiological conditions and provide opportunities to increase production if necessary, e.g., during blood loss or infections, a process known as “stress” or “emergency” hematopoiesis4, 5. Furthermore, extracellular signals can direct differentiation of hematopoietic progenitors into specific lineages. Growth factors that play a major role in this process are thrombopoeitin (TPO), essential for platelet production, erythropoietin (EPO), regulating the production of erythrocytes, and colony stimulating factors (CSFs), involved in myeloid cell development2, 6-8. The majority of leukocytes in the peripheral blood are neutrophilic granulocytes or neutrophils, which are essential for the early, aspecific immune response against microorganisms. The process of neutrophilic development is known as myelopoiesis. During this process, HSCs develop through a number of differentiation stages, i.e., myeloblasts, promyelocytes, neutrophilic myelocytes, neutrophilic metamyelocytes and neutrophilic band cells into mature neutrophils.
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| The work presented in this thesis was performed at the Department of Hematology at the Erasmus Medical Center in Rotterdam and was financially supported by the Center for Translational Molecular Medicine (CTMM), the Dutch Cancer Society “Koningin Wilhelmina Fonds” (KWF Kankerbestrijding), the Netherlands Genomics Initiative (NGI) and the ERA-Net for Research Programmes on Rare Diseases (E-RARE). Printing of this thesis was financially supported by de MPN Stichting - Fonds Wetenschappelijk Onderzoek, the Erasmus University Rotterdam, de J.E. Jurriaanse Stichting, Biozym TC B.V. and Integrated DNA Technologies. | |
| I.P. Touw (Ivo) | |
| Erasmus University Rotterdam | |
| hdl.handle.net/1765/38481 | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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Beekman, R. (2013, January 18). Genome-Wide Analysis of Severe Congenital Neutropenia and Leukemia Implications for leukemogenesis. Retrieved from http://hdl.handle.net/1765/38481 |
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