The Effect of ۵ Mand ۱۰ MBenzoquinone on CXCL۱۲ and KITLG Genes Expression in Mesenchymal Stem Cells

Background: Chronic exposure to benzene or its derivative (benzoquinone and hydroquinone) in humans may result in bonemarrow damage followed by development of leukemia. Induction of extra cellular signaling pathways in microenvironment ofbone marrow of patients with acute myeloid leukemia (AML) may lead to progression of disease and treatment resistance. Mesenchymalstromal cells (MSCs) are a subpopulation of multipotent cells of non-haematopoietic origin. They are increasingly recognizedas a central component of the bone marrow (BM) microenvironment that contributes to the structure and function of theBMniche. MSCs play significant roles in regulation of homing, self-renewal, differentiation, and proliferation of hematopoietic stemcells (HSC) through production of various crucial elements in hematopoietic niche. Niches are local tissue microenvironments thatmaintain and regulate stem cells. Previous studies have shown that benzene is one of the important risk factors for AML.Objectives: This study aimed to evaluate the effect of low doses of benzoquinone on the expression levels of some hematopoieticfunction related genes including CXCL۱۲ and Kit ligand (KITLG) in MSCs.Methods: MSCs obtained from bone marrow mononuclear cells of healthy volunteer and cultured in the proper medium. Aftercharacterization with standard methods, MSCs were exposed to two doses of ۵ and ۱۰ micro molar ( M) of benzoquinone; then, theexpression of KITLG and CXCL۱۲ genes were evaluated by real time PCR method.Results: The results indicated that the expression of KITLG and CXCL۱۲ genes were increased after treatment with benzoquinone,specifically with ۵ Mdose.Conclusions: The results of our study along with well-established role of KITLG/SCF signaling pathways and the CXCL۱۲-CXCL۴ axisin maintenance of the niche and cancer development, benzene metabolite, benzoquinone, is among the major factors in causingacute myelogenous leukemia.

Keywords:

Benzene , Kit Ligand , CXCL۱۲ , Chemokine