Transcriptional Regulation and Epigenetics

Leukaemias

Another area of research is the development of model systems to study leukaemia. Leukaemias are a group of diseases resulting in the abnormal production of any type of white blood cell. Several causes have been implicated in the disease progression including the repositioning of part of one chromosome next to part of another chromosome during cell division (chromosomal translocation). This, results in the production of an abnormal protein, which consists of part of one protein fused to part of another protein, some of these chimeric proteins have the ability to activate cells in the absence of growth factors and drive differentiation along a specific cell lineage. We are therefore developing model systems to differentiate mouse embryonic stem cells to specifically form either myeloid or lymphoid white blood cells. These models can then be used to study the processes involved in leukaemogenesis.

Figure 1. System for modelling early events in leukaemia.

Undifferentiated Mouse Embryonic stem cells (left) have high levels of an enzyme called alkaline phosphates-which can be detected using a specific dye which turns the cells red. Using specific growth factors, each single ES cell can be directed to form an embryoid body (right). These balls of cells contain cells of the three germ layers which make up all the different cell types of the body (Ectoderm, Mesoderm & Endoderm) embryonic stem cells therefore have the potential to form all cell types of the body. From these Haematopoietic Stem Cells can be formed.