PMID- 21933581 OWN - NLM STAT- MEDLINE DCOM- 20120427 LR - 20181201 IS - 2542-5641 (Electronic) IS - 0366-6999 (Linking) VI - 124 IP - 16 DP - 2011 Aug TI - Matrix metalloproteinase-9 was involved in the immuno-modulatory defect of mesenchymal stem cell from chronic myeloid leukemia patients. PG - 2423-30 AB - 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. FAU - Zhu, Xi-Shan AU - Zhu XS AD - 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 FAU - Shi, Wei AU - Shi W FAU - An, Guang-Yu AU - An GY FAU - Zhang, Hong-Mei AU - Zhang HM FAU - Song, Yu-Guang AU - Song YG FAU - Li, You-Bin AU - Li YB LA - eng PT - Journal Article PL - China TA - Chin Med J (Engl) JT - Chinese medical journal JID - 7513795 RN - 0 (Antigens, CD34) RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Adolescent MH - Adult MH - Antigens, CD34/genetics/metabolism MH - Apoptosis/drug effects MH - Blotting, Western MH - Cell Cycle/drug effects MH - Cells, Cultured MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Flow Cytometry MH - Fusion Proteins, bcr-abl/genetics/metabolism MH - Humans MH - Immunomodulation MH - In Situ Hybridization, Fluorescence MH - Karyotype MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*enzymology/*immunology/metabolism MH - Male MH - Matrix Metalloproteinase 9/genetics/*metabolism MH - Mesenchymal Stem Cells/cytology/*immunology MH - Middle Aged MH - Platelet Endothelial Cell Adhesion Molecule-1/genetics/metabolism MH - T-Lymphocytes MH - Vascular Endothelial Growth Factor Receptor-2/genetics/metabolism MH - Young Adult EDAT- 2011/09/22 06:00 MHDA- 2012/04/28 06:00 CRDT- 2011/09/22 06:00 PHST- 2011/09/22 06:00 [entrez] PHST- 2011/09/22 06:00 [pubmed] PHST- 2012/04/28 06:00 [medline] PST - ppublish SO - Chin Med J (Engl). 2011 Aug;124(16):2423-30.