G-CSF in the Biology and Treatment of Acute Myeloid Leukemias

Abstract

Granulocyte colony-stimulating factor (G-CSF) is an hemopoietic growth factor produced by fibroblasts, monocytes and endothelial cells. The role of G-CSF in the biology of acute myeloid leukemia (AML) has been investigated by several authors, who have demonstrated receptor mediated enhanced proliferation of AML blasts in vitro, in the presence of G-CSF. This effect is further increased by addition of other cytokines such as GM-CSF, IL3, IL4, Stem cell factor (SCF), while Tumor Necrosis Factor (TNF) and Transforming Growth Factor β1 (TGF β1) seem to exert an inhibitory activity. An autocrine production of G-CSF by AML cells, a paracrine production by accessory cells and a protective effect displayed by G-CSF against programmed cell death could partially contribute to explain the pathogenesis of AML. In vivo, G-CSF has been used after chemotherapy in AML, in order to improve hemopoietic recovery in patients at high risk of infection. Current studies are focusing on better definition of the role of G-CSF, as such or combined with other biological modifiers, in dose intensification and autologous bone marrow or peripheral blood stem cell transplantation.

Key Words:

• growth factors
• granulocyte colony-stimulating factor
• acute myeloid leukemia
• neutrophils
• chemotherapy