Abstract OBJECTIVE: To study the protective effect of bone marrow stromal cells (BMSCs) upon childhood leukemia cells and the influence of VLA-4 antibody in vitro on leukemia cell apoptosis. METHODS: BMSCs from children with acute leukemia-were isolated by human lymphocyte separation medium. BMSCs (adherent) and leukemia cells (suspended) were cultured in vitro. This study included four groups: leukemia cells alone (control), leukemia cells+BMSCs, leukemia cells+BMSCs supernatant and leukemia cells+BMSCs+VLA-4 antibody. The apoptosis rate of leukemia cells in the four groups was determined by Annexin Ⅴ-FITC double-labeled flow cytometry. The expression of survivin and bcl-2 genes in leukemia cells was ascertained by RT-PCR. RESULTS: The apoptosis rate of leukemia cells in the leukemia cells+BMSCs and the leukemia cells+BMSCs supernatant groups was lower than that in the control group (P<0.05). Compared with the leukemia cells+BMSCs and the leukemia cells+BMSCs supernatant groups, the apoptosis rate of leukemia cells in the VLA-4 antibody group increased significantly (P<0.05). In the VLA-4 antibody group, the apoptosis rate of leukemia cells increased with prolonged culture time. There were significant differences in the apoptosis rate between 12 hrs and 24 hrs after VLA-4 antibody treatment (P<0.01). The expression of survivin and bcl-2 genes in leukemia cells from the VLA-4 antibody groups was reduced compared with that from the leukemia cells+BMSCs and the leukemia cells+BMSCs supernatant groups (P<0.05). CONCLUSIONS: BMSCs play protective roles on leukemia cells. VLA-4 antibody can block the adhesion between BMSCs and leukemia cells and promote leukemia cell apoptosis.［Chin J Contemp Pediatr, 2010, 12 (11):897-901］
LI Zhong-Xia,JIA Xiu-Hong,LI Jian-Chang et al. Effects of bone marrow stromal cells and VLA-4 antibody on apoptosis of childhood leukemia cells[J]. 中国当代儿科杂志, 2010, 12(11): 897-901.
LI Zhong-Xia,JIA Xiu-Hong,LI Jian-Chang et al. Effects of bone marrow stromal cells and VLA-4 antibody on apoptosis of childhood leukemia cells[J]. CJCP, 2010, 12(11): 897-901.
［1］Crowther CA, Haslam RR, Hiller JE, Doyle LW, Robinson JS. Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial［J］. Lancet, 2006, 367(9526):1913-1919.
［2］Pongracz JE, Stockley RA. Wnt signalling in lung development and diseases［J］. Respir Res, 2006, 7(1):15.
［3］Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins［J］. Growth Factors, 2004, 22(4):233-241.
［4］Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-β family signalling［J］. Nature, 2003, 425(6958): 577-584.
［5］Warburton D, Bellusci S, De Langhe S, Del Moral PM, Fleury V, Mailleux A, et al. Molecular mechanisms of early lung specification and branching morphogenesis［J］. Pediatr Res, 2005, 57(5):26-37.
［6］Sebald W, Nickel J, Zhang JL, Mueller TD. Molecular recognition in bone morphogenetic protein (BMP)/receptor interaction［J］. Biol Chem, 2004, 385(8):697-710.
［9］Eblaghie MC, Reedy M, Oliver T, Mishina Y, Hogan Bl. Evidence that autocrine signaling through Bmpr1a regulates the proliferation,survival and morphogenetic behavior of distal lung epithelial cells［J］. Dev Biol, 2006, 291(1):67-82.
［10］Beppu H, Kawabata M, Hamamoto T, Chtil A, Minowa O, Noda T, et al. BMP type II receptor is required for gastrulation and early development of mouse embryos［J］. Dev Biol, 2000, 221(1):249-258.
［11］Chen C, Chen H, Sun J, Bringas P Jr, Chen Y, Warburton D, et al. Smad1 expression and function during mouse embryonic lung branching morphogenesis［J］. Am J Physiol Lung Cell Mol Physiol, 2005, 288(6):1033-1039.
［12］Hai T, Hartman MG. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis［J］. Gene, 2001, 273(1):1-11.
［13］Joyce DA,Gimblett G, Steer JH. Targets of glucocorticoid action on TNF-α release by macrophages［J］. Inflamm Res, 2001, 50(7):337-340.
［14］Monzen K, Hiroi Y, Kudoh S, Akazawab H, Okaa T, Takimotoa E, et al. Smads, TAK1, and their common target ATF-2 play a critical role in cardiomyocyte differentiation［J］. J Cell Biol, 2001,153(4):687-698.
