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Normal and neoplastic stem cells

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Self renewal is the principal property that distinguishes stem cells from their daughter cells; when stem cells divide as a population they give rise to stem cells by self renewal, and progenitors by differentiation. The balance between self renewal and differentiation is what generates and then maintains tissues, and enables them to respond to injury or other stressors. Studies identifying hematopoietic stem cells and progenitors have made hematopoiesis one of the best systems for studying the molecular changes in cell fate decision making, and oncogenesis. Further, it serves as a paradigm for finding preclinical and clinical platforms for tissue and organ replacement and regeneration. Stem cell isolation and transplantation is the basis for regenerative medicine. Self renewal is dangerous, and therefore strictly regulated. Poorly regulated self renewal can lead to the genesis of cancer, and within it, cancer stem cells, the self renewing subset of cells within a cancer. At the very least, all cancer stem cells within a cancer are the target of therapeutic elimination. This prediction necessitates a profoundly different approach to cancer research, compelling investigators to prospectively isolate cancer stem cells in order to assess both genomic and epigenomic events in the cancer stem cell pool, as well as assign molecular pathways regulating their behavior. In the hematopoietic lineage, it is possible to find both the leukemia stem cells for such analyses, and to chart the progression from normal hematopoiesis to leukemia. While many events, genetic and epigenetic could play a role in cancer progression, this allows investigators to find out how the cancer has done it. This lecture will consider in more depth the role of programmed cell removal as an obstacle that must be overcome for cancer clones to succeed, and how the molecular targets revealed by it provide one avenue to cancer therapy.

This talk is part of the MRC LMB Seminar Series series.

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