title: Matrix metalloproteinase-9 was involved in the immuno-modulatory defect of mesenchymal stem cell from chronic myeloid leukemia patients.
abstract: BACKGROUND
  Overwhelming evidences on chronic myeloid leukemia (CML) indicate that patients harbor quiescent CML stem cells that are responsible for blast crisis. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated.
  
  
  METHODS
  We have previously isolated fetal liver kinase-1-positive (Flk1(+)) cells carrying the BCR/ABL fusion gene from the bone marrow of Ph(+) patients with hemangioblast property. In this study, we isolated CML patient-derived Flk1(+)CD31(-)CD34(-) mesenchymal stem cells (MSCs) and detected their biological characteristics and immunological regulation using fluorescence in situ hybridization (FISH) analysis, fluorescence activated cell sorting (FACS), enzyme-linked immunoadsorbent assay, mixed lymphocyte reaction assays; then we compared these characters with those of the healthy donors.
  
  
  RESULTS
  CML patient-derived Flk1(+)CD31(-)CD34(-) MSCs had normal morphology, phenotype and karyotype while appeared impaired in immuno-modulatory function. The capacity of patient Flk1(+)CD31(-)CD34(-) MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro.
  
  
  CONCLUSIONS
  CML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than hematopoietic stem cells (HSCs). MSCs might be a potential target for developing efficacious treatment for CML.
authors.affiliation: Institute of Internal Oncology, Center of Tumor Research and Therapy, Beijing Shijitan Hospital, Capital Medical University (the Ninth Medical College of Peking University), Beijing 100038, China. mountain.red@163.com
authors.forename: Xi-Shan
authors.initials: XS
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: An
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zhang
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: Song
authors.forename: You-Bin
authors.initials: YB
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D016044:Fusion Proteins, bcr-abl; D020780:Matrix Metalloproteinase 9