The Expression of SREBF1 Inducing By Dexamethasone Promotes Bone Marrow Mesenchymal Stromal Cells Differentiate to Adipocytes to Attract and Protect the Residual T-Cell Acute Lymphoblastic Leukemia Cells

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood malignant disorder with high rate of relapse. The patients relapse as a result of minimal residual disease (MRD), which is originated from residual T-ALL cells in the bone marrow microenvironment (BMM). In the present study, we observed that adipocytes increased dramatically in BMM of T-ALL patients after being exposed to chemotherapeutic drugs. Then, we proved adipocytes attracted T-ALL cells by releasing CXCL13 and supported leukemia survival by activating Notch1 signaling pathway via DLL1 and Notch1 binding. Furthermore, we verified that DEX induced adipogenic differentiation by enhancing the expression of SREBF1 in BMSCs, and SREBF1 inhibitor significantly decreased adipogenic potential of BMSCs and the following ability of adipocytes to support T-ALL cells in vitro and in vivo. These findings confirmed that differentiation of BMSCs to adipocytes induced by DEX contributed to MRD of T-ALL and provided an auxiliary clinical treatment to reduce the recurrence rate of it.