title: Resistance of leukemic stem-like cells in AML cell line KG1a to natural killer cell-mediated cytotoxicity.
abstract: Leukemic stem cells (LSCs) play the central role in the relapse and refractory of acute myeloid leukemia (AML) and highlight the critical need for the new therapeutic strategies to directly target the LSC population. However, relatively little is known about the unique molecular mechanisms of drug and natural killer cells (NK)-killing resistance of LSCs because of very small number of LSCs in bone marrow. In this study, we investigated whether established leukemia cell line contains LSCs. We showed that KG1a leukemia cell line contained leukemic stem-like cells, which have been phenotypically restricted within the CD34(+)CD38(-) fractions. CD34(+)CD38(-) cells could generate CD34(+)CD38(+) cells in culture medium and had renewal function. Moreover, CD34(+)CD38(-) cells had self-renewal potential. We found that leukemic stem-like cells from KG1a cells were resistant to chemotherapy and NK-mediated cytotoxicity. NKG2D ligands involve in protecting LSCs from NK-mediated attack. Taken together, our studies provide a novel cell model for leukemic stem cells research. Our data also shed light on mechanism of double resistant to chemotherapy and NK cell immunotherapy, which was helpful for developing novel effective strategies for LSCs.
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China. shemiaorong@hotmail.com
authors.forename: Miaorong
authors.initials: M
authors.lastname: She
authors.forename: Xinqing
authors.initials: X
authors.lastname: Niu
authors.forename: Xilin
authors.initials: X
authors.lastname: Chen
authors.forename: Jinggao
authors.initials: J
authors.lastname: Li
authors.forename: Maohua
authors.initials: M
authors.lastname: Zhou
authors.forename: Yanjie
authors.initials: Y
authors.lastname: He
authors.forename: Yi
authors.initials: Y
authors.lastname: Le
authors.forename: Kunyuan
authors.initials: K
authors.lastname: Guo
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology*
chemical_list: D018952:Antigens, CD34; D051997:ADP-ribosyl Cyclase 1