LAUSR

Mesenchymal stem cells (MSCs) are one of the most prominent cells in the bone marrow. MSCs can affect acute lymphocytic leukemia (ALL) cells under hypoxic conditions. For this aim, we used MOLT-4 cells as simulators of ALL cells co-cultured with bone marrow mesenchymal stem cells (BMMSCs) under hypoxic conditions in-vitro. Then, mRNA and protein expression of the MAT2A, PDK1, and HK2 genes were evaluated by real-time PCR and western blot which also followed by apoptosis measurement by a flow-cytometric method. Next, the methylation status of the target genes was investigated by MS-qPCR. Additionally, candidate gene expressions were examined after treatment with rapamycin using MTT assay. We found that the mRNA expression of the candidate genes was augmented under the hypoxic condition in which MAT2A was up-regulated in co-cultured cells compared to MOLT-4, while HK2 and PDK1 were down-regulated. Moreover, we found an association between gene expression and promoter methylation levels of target genes. Besides, expressions of the candidate genes were decreased, while their methylation levels were promoted following treatment with rapamycin. Our results suggest an important role for the BMMSC in regulating the methylation of genes involved in cell survival in hypoxia conditions; however, we found no evidence to prove the MSCs' effect in directing malignant lymphoblastic cells to apoptosis. This article is protected by copyright. All rights reserved.