title: Evidence that high-migration drug-surviving MOLT4 leukemia cells exhibit cancer stem cell-like properties.
abstract: Leukemia represents a spectrum of hematological malignancies threatening human health. Resistance to treatments and metastasis of leukemia are the main causes of death in patients. Leukemia stem cells (LSCs) are the initiating cells of leukemia as well as the main source of drug resistance, invasion and metastasis. Consequently, eliminating LSCs is a prerequisite to eradicate leukemia. Preliminary studies in our laboratory have shown that chemokines and their related receptors play an important role in the drug resistance and metastasis of leukemic cells. In this study, we obtained high migration drug-surviving (short term) MOLT4 cells (hMDSCs-MOLT4) with treatment of doxorubicin (DOX) after Transwell assay. Then we detected stem cell-associated molecular markers on hMDSCs-MOLT4 cells and the parental MOLT4 cells by FCM, QPCR, western blotting, H&E staining and immunohisto-chemistry experimental techniques in vitro and in vivo. Moreover, we explored its impact on drug resistance and tumor formation. Then we found that compared with the parental MOLT4 cells, the mRNA expression levels of stem cell-related factors Sox2, Oct4, C-myc, Klf4, Nanog, Bmi-1, CXCR4 are increased in hMDSCs-MOLT4 cells, together with the protein expression levels of Sox2, Oct4, Klf4, Nanog, CXCR4 and CD34. Our results indicated that hMDSCs-MOLT4 cells exhibited strong drug resistance and certain cancer stem cell-like characteristics. It is the first indication that the targeting stemness factors such as Sox2, Oct4, Klf4, Nanog and CXCR4 may represent plausible options for eliminating T-ALL stem-like cells. The present findings shed light on the relationship between drug-tolerant leukemic cells and cancer stem cells.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xiong
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Chaohua
authors.initials: C
authors.lastname: Deng
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei 430000, P.R. China.
authors.forename: Changqing
authors.initials: C
authors.lastname: An
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Hao
authors.affiliation: Hubei University of Technology Engineering and Technology College, Wuhan, Hubei 430000, P.R. China.
authors.forename: Xiangyong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Xinzhou
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Ruijing
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000090062:Kruppel-Like Factor 4; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D009363:Neoplasm Proteins; D004317:Doxorubicin