Bone marrow stromal cells in the pathogenesis of acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is clonal disorder affecting pluripotent stem cell and characterized by ineffective hematopoiesis. Genetic abnormalities in a progenitor cells is thought to lead to uncontrolled growth of leukemia cells. In addition, in the last years, it has been clearly recognized that the hematopoietic microenvironment (HM) plays an important role in the pathogenesis of AML. The HM can regulate hematopoiesis by interacting directly with HC and/or by secreting regulatory molecules that exert a positive or negative influence on the growth of HC. Stromal elements are important in the homing of immature HC or hematopoietic stem cells. Several studies propose that important quantitative and functional alterations are present in the BMSC of AML patients. AML may arise in the setting of an abnormal HM, resulting in the generation of multiple populations with varying initiation event. Dysfunction of HM may contribute to leukemia by supplying abundant growth factors that promote proliferation and/or inhibit apoptosis. Recent discoveries utilizing mouse models showed that genetic alteration in cells of HM can induce AML.