Background: Chronic exposure to benzene or its derivative (benzoquinone and hydroquinone) in humans may result in bone marrow damage followed by development of leukemia. Induction of extra cellular signaling pathways in microenvironment of bone marrow of patients with acute myeloid leukemia (AML) may lead to progression of disease and treatment resistance. Mesenchymal stromal cells (MSCs) are a subpopulation of multipotent cells of non-haematopoietic origin. They are increasingly recognized as a central component of the bone marrow (BM) microenvironment that contributes to the structure and function of theBM niche. MSCs play significant roles in regulation of homing, self-renewal, differentiation, and proliferation of hematopoietic stem cells (HSC) through production of various crucial elements in hematopoietic niche. Niches are local tissue microenvironments that maintain 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 hematopoietic function related genes including CXCL12 and Kit ligand (KITLG) in MSCs.
Methods: MSCs obtained from bone marrow mononuclear cells of healthy volunteer and cultured in the proper medium. After characterization with standard methods, MSCs were exposed to two doses of 5 and 10 micro molar (ɱM) of benzoquinone; then, the expression of KITLG and CXCL12 genes were evaluated by real time PCR method.
Results: The results indicated that the expression of KITLG and CXCL12 genes were increased after treatment with benzoquinone, specifically with 5 ɱMdose.
Conclusions: The results of our study along with well-established role of KITLG/SCF signaling pathways and the CXCL12-CXCL4 axis in maintenance of the niche and cancer development, benzene metabolite, benzoquinone, is among the major factors in causing acute myelogenous leukemia.