The molecular heterogenity of MLL-rearranged pediatric AML

Continuous renewal of blood cells, so called hematopoiesis, is essential for human life. Starting from several months after birth the majority of blood cell production occurs in the bone marrow. Circulating blood cells are of diverse morphology and function and can be divided in red blood cells (erythrocytes), white blood cells (leukocytes), and platelets. The need for continuous production of blood cells is explained by the fact that the majority of mature blood cells have limited life span, i.e. erythrocytes live about 100-120 days and platelets only 5-9 days. All new blood cells arise from the self-renewing hematopoietic stem cell (HSC), which resides in the bone marrow. These HSCs produce daughter cells by cell division, thereby maintaining the stem cell population as well as creating offspring that can differentiate into more committed progenitors. Under strict regulation, these committed common lymphoid or myeloid progenitors, differentiate into mature blood cells (Figure 1) and are released in the peripheral blood. In the process of differentiation the blood cells gain specific functions for their mature life (such as the possibility to bind oxygen for the erythrocyte) but loose the capacity to proliferate. This shifting balance is essential for the body to keep control of the number of circulating blood cells.

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