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Normal haemopoiesis

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In the adult, normal haemopoiesis occurs predominantly in the bone marrow, although haemopoietic stem cells circulate in the blood stream and the potential for haemopoiesis in liver, spleen or other tissues is retained. All blood cells are derived ultimately from a pluripotent haemopoietic stem cell, able to give rise to lymphoid and myeloid lineages [1]. The pluripotent stem cells are capable not only of renewal but also of generating multipotent myeloid stem cells and common lymphoid stem cells (Fig. 1.1). The multipotent stem cell gives rise in turn to committed progenitor cells from which cells of the major myeloid lineages are derived. Differentiation and maturation are controlled by a variety of cytokines which are to some extent specific for particular cell lines. In addition, the microenvironment and accessory cells such as fibroblasts, osteoblasts and fat cells have a role in the differentiation and maturation of stem cells. Cells of haemopoietic origin include mast cells and osteoclasts.

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Figure 1.1

A diagram of the stem cell hierarchy and myeloid and lymphoid differentiation pathways. Abbreviation: NK, natural killer.

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The nature of leukaemia and leukaemogenesis

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Leukaemia may be viewed as a cancer of the blood and derives its name from the German term, leukämie, coined by Rudolf Virchow in 1848 and meaning 'white blood', from the Greek λευκος - leukos, white and αιμα - haima, blood. Although initially recognized as a disease affecting the blood, leukaemia is in fact a disease that usually originates in the bone marrow. Leukaemia arises by an acquired somatic mutation in a single cell, giving that cell and its progeny some advantage over normal polyclonal cells, which are gradually replaced by leukaemic cells. In common with other neoplasms, leukaemia can thus be viewed as an acquired genetic disease in the sense that it results from genetic alteration in the cell that gives rise to the leukaemic clone. The host immune response also has a role in disease development, since the body's immune response includes some ability to recognize tumour cells and destroy them.

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Myeloid neoplasms arise by mutation of a haemopoietic stem cell or a progenitor cell that has acquired stem cell characteristics (Fig. 1.2). Many neoplasms, including most types of acute myeloid leukaemia (AML) and the myelodysplastic syndromes (MDS), arise from a mutated multipotent stem cell. It is possible that some subtypes of AML arise by mutation of a committed progenitor cell without the capacity to differentiate into cells of erythroid or megakaryocyte lineages. Some chronic myeloid leukaemias arise from mutation in a pluripotent stem cell so that at one stage of the disease the leukaemia may manifest itself as a lymphoid leukaemia or lymphoma. This is true of Philadelphia (Ph)-positive chronic myeloid leukaemia associated with a BCR-ABL1 fusion gene (in which B-lineage and less often T-lineage ...

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