MicroRNAs in Pediatric Acute Lymphoblastic Leukemia: Small players with huge potential

Hematopoiesis is a dynamic balance of cellular proliferation, survival, apoptosis and differentiation in which the pluripotent hematopoietic stem cell gives rise to lymphoid and myeloid precursors of blood cells. The B-lymphoid precursor sequentially differentiates from proB-cells into common/preB-cells and fi nally yields mature B-lymphocytes. The T-lymphoid precursor generates thymocytes or proT-cells that further differentiate into T-lymphocytes. The myeloid precursor gives rise to granulocytes, monocytes, platelets and erythrocytes. This process is under tight surveillance by regulators including transcription factors, cytokines and growth factors. In case of defects in surveillance and/or oncogenic hits in the maturing hematopoietic cell, cells may arrest at different levels of maturation. Leukemia cells grow exponentially with limited differentiation thereby suppressing the development of normal blood cells in the bone marrow. As a consequence leukemia patients suffer from fatigue (shortage of erythrocytes or anemia), infections (shortage of mature lymphocytes and granulocytes) and bleeding (low platelet numbers). Despite the fact that multiple consecutive events are required for the development of leukemia, the clinical symptoms associated with acute leukemia occur rather abrupt and the progression of the disease is very fast if not treated instantly.

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