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PhD ceremony Ms. K. Klauke: Epigenetic regulation of normal and malignant hematopoiesis

When:We 23-10-2013 at 16:15

PhD ceremony: Ms. K. Klauke, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Epigenetic regulation of normal and malignant hemotopoiesis

Promotor(s): prof. G. de Haan

Faculty: Medical Sciences

Stem cells are required for the formation of all cells in our body throughout our entire lifespan. They were discovered in almost every organ. These cells have the unique capacity to self-renew relatively unlimited, producing two stem cells upon division. In addition, stem cells can specialize (differentiate) into the mature cells of which the tissue is composed. A precise balance between self-renewal and differentiation of HSCs is essential to maintain a proper-sized HSC pool throughout life. Unbalanced stem cell divisions can result in diseases, such as cancer.

A protein complex has been identified that acts as a switch to determine the fate of blood stem cells. The so-called ' Polycomb complex’ can modify the manner in which the DNA is packed in the nucleus of stem cells, which determines the genetic information in the DNA that is used for the function of the cell. Polycomb proteins function together in a large protein complex. The proteins compete with each other for every position in the complex. Depending on which proteins integrate into the complex , stem cells self-renew or specialize in mature blood cells. In this way, the complex functions as a 'switch'. This discovery is a step forward in understanding the balance between health and disease . If the switch results in too much renewal of stem cells leukemia can develop (blood cancer). If the switch results in too much maturation and loss of stem cells, blood cell deficiency might occur.

By manipulation of this protein complex, and by marking individual stem cells with a ‘barcode’, this study also gave more insight into the development and the heterogeneity of leukemia. Leukemia can be maintained by multiple ‘leukemia stem cells’ (mother cells that produce the bulk tumour cells)with different properties with respect to growth rate and differentiation. These leukemia stem cells can also react differently to stresses, such as chemotherapy. This study therefore highlights the usefulness of combination therapy with multiple chemotherapeutic agents to treat leukemia.

The results of this research have been published in Nature Cell Biology

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