The t(4;11) fusion protein MLL/AF4 regulates telomerase reverse transcriptase (TERT) expression

Abstract

The human blood consists of many different kinds of blood cells. There are the red blood cells (erythrocytes) and the white blood cells (leukocytes), further subdivided into blood cells like lymphocytes, granulocytes, monocytes etc. Those cell types have all different purposes ranging from transportation, wound healing or support of the immune system. The erythrocytes are for transportation and carry the oxygen or carbon dioxide through the blood stream. White blood cells or leukocytes include various cell types divided into four sub groups. Group one are the granulocytes containing neutrophils, eosinophils and basophils which destroy invading bacteria or parasites, secrete histamine and play a role in modulating allergic inflammation reactions. Group two consists of the monocytes which infiltrate the blood vessel surrounding tissue and differentiate to macrophages to fight pathogens or destroy damaged cells. The third group are the lymphocytes which consist of B-cells, mainly antibody producers, T-cells which play an important role in inflammation and regulating other immune cells. The last cell type in this group is the natural killer cell (NK-cell). NK cells kill virus infected cells and have been reported to kill gastric tumour cells (Miller, 2001). There are also thrombocytes in the blood which are small cell fragments produced by megakaryocytes in the bone marrow. On the other hand they support wound healing and coagulation. All of these blood cells are derived from pluripotent haematopoietic stem cells (HSC) in the bone marrow. Pluripotent stem cells create progenitor cells with a predetermined fate (Figure 1-1). HSCs are generated by a process called haematopoiesis and have been classified depending on their capacity to self-renew. In the beginning there are long-term self renewing HSCs which generate then other more short living HSCs resulting in pluripotent progenitors without self-renewal capacity (Reya et al., 2001). HSCs occupy niches in the bone marrow. A niche is a microenvironment which consists of supporting cells providing necessary cytokines for self renewal and differentiation ability (Yin and Li, 2006). 3 The differentiation process of a HSC can result in a myeloid or a lymphoid progenitor cell. Following the lineage determination a series of differentiation steps leads first to the progenitor cell and then to a precursor cell. Progenitor cells still divide at a high rate, although numbers of cell divisions are limited. Continued differentiation of the precursors finally produces the fully differentiated and mature blood cell (Alberts, 2002). In summary it can be stated that the haematopoiesis of HSCs is a delicate and a critical sequence of incidents with highly and tightly regulated processes. These processes are proliferation, maturation and differentiation. The tight regulation is necessary as for example many leukocytes are very short living and need to be replaced constantly. The half life of neutrophils in the peripheral blood for example lies between 8 and 10 hours which means there have to be ensured strictly controlled mechanisms for proper differentiation during the 10 to 14 days of their maturation. This maintains a constant level of neutrophils in the peripheral blood (Speck, 2001). Disruption of this process can lead to a disordered form of haematopoiesis called leukaemia, the cancer of the blood.