MicroRNAs in Pediatric Acute Lymphoblastic Leukemia: Functions and Targets

Abstract

All different types of circulating blood cells originate from hematopoietic stem cells (HSCs). The pluripotential HSCs have the capacity of self-renewal, which provides the body with a secure backup of HSCs. HSCs can also differentiate into progenitor cells, which can further differentiate to different types of blood cells. This continuous process of blood cell production mainly happens in the bone marrow and is called “hematopoiesis”. At the first step of hematopoiesis two distinct populations of cells are generated: common lymphoid progenitors and common myeloid progenitors. As shown in Figure 1, these common progenitors give rise to a variety of mature blood cells via several processes: thrombopoiesis (to produce thrombocytes), erythropoiesis (to produce erythrocytes), granulopoiesis (to produce basophils, neutrophils and eosinophils), monopoiesis (to produce monocytes and then macrophages and myeloid dendritic cells) and lymphopoiesis (to produce B-cells, T-cells and natural killer cells). During hematopoiesis, the differentiated cells lose their proliferative potential but gain more functionality. This is a crucial process, which keeps the number of circulating blood cells under control. Division and differentiation of hematopoietic cells are controlled by several regulators such as epigenetic modifiers, transcription factors, posttranscriptional modulators, cytokines and growth factors. Disruption in hematopoiesis may lead to a differentiation arrest and excessive growth of immature blood cells, which are called "blasts". Acute leukemia (leukos and haima means white and blood in Greek, respectively) is a disease of uncontrolled high proliferation of the blasts and classified according to the lineage origin of the blasts (lymphoid or myeloid). In addition, leukemia with slow onset and slow progression is called "chronic leukemia".