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With this aim, we used MOLT\u20104 cells as simulators of ALL cells cocultured 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\u2010time PCR and Western blot which was also followed by apoptosis measurement by a flow\u2010cytometric method. Next, the methylation status of the target genes was investigated by MS\u2010qPCR. Additionally, candidate gene expressions were examined after treatment with rapamycin using 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyltetrazolium bromide (MTT) assay. We found that the mRNA expression of the candidate genes was augmented under the hypoxic condition in which MAT2A was upregulated in cocultured cells compared to MOLT\u20104, while HK2 and PDK1 were downregulated. 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 on directing malignant lymphoblastic cells to apoptosis.<\/jats:p>","DOI":"10.1002\/bab.2154","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T08:11:53Z","timestamp":1617178313000},"page":"822-839","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Under hypoxic conditions, MSCs affect the expression and methylation level of survival\u2010related genes in ALL independent of apoptosis pathways in vitro"],"prefix":"10.1002","volume":"69","author":[{"given":"Faroogh","family":"Marofi","sequence":"first","affiliation":[{"name":"Department of Hematology, Division of Immunology, Faculty of Medicine Tabriz University of Medical Sciences  Tabriz Iran"},{"name":"Immunology research center Tabriz 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