8 Apoptosis, haemopoiesis and leukaemogenesis*

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Apoptosis, or physiological cell death, is the way in which unwanted cells are removed. The majority of cells formed during haemopoiesis are destined to die by apoptosis before they are fully differentiated, and homeostasis of cell number is maintained by a balance between mitosis and apoptosis. Many haematological malignancies are associated with changes in the number of cells undergoing apoptosis, which may be a direct or an indirect effect. Genetic mutations that prevent cell death cause cells to accumulate and can eventually lead to malignancy. Alternatively, oncogenic mutations that lead to increased cell production can indirectly cause a decrease in apoptosis in some populations and an increase in others. Chemotherapeutic drugs may kill cells directly, or indirectly by inducing apoptosis as a stress response. Therapeutic strategies are evolving to increase the propensity of malignant cells to die by either means and to mitigate side effects by reducing apoptosis in non-malignant cells.

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  • Cited by (14)

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      In addition, the bone marrow microenvironment provides a primary site in which residual leukemic cells may survive standard chemotherapy [35]. Because inducing apoptosis is the main mechanism for many chemotherapeutic drugs to inhibit the growth of leukemic cells [36–38], using chemotherapy drugs that can induce apoptosis in leukemic cells may enhance the anti-tumor effect on highly proliferative Jurkat cells. In light of this, we examined the cytotoxicity of MTX on Jurkat cells co-cultured with leukemic BMSCs.

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      2003, Biochemical and Biophysical Research Communications
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      Over-expression of other active serine proteases, for example proteinase K, also results in apoptosis [59], but in this case cell death is clearly not the physiological role of the protease. The analysis of the role of putative apoptotic proteins is complicated because apoptosis is a common response to cell stress [60]. Over-expression or deletion of genes, addition of drugs or physical changes to a cell’s environment often provokes an apoptotic stress response.

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    *

    Dr Ekert is supported by an NH and MRC post-graduate medical research fellowship. Dr Vaux is supported by the Anti-Cancer Council of Victoria and the Cancer Research Institute of New York.

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